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Bone & Joint Research
Vol. 13, Issue 12 | Pages 703 - 715
3 Dec 2024
Raza IGA Snelling SJB Mimpen JY

Aims. Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease. Methods. A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed. Results. A total of 161 studies were included, which covered capsule, ligaments, meniscus, skeletal muscle, synovium, and tendon in both humans and animals, and fat pad and intervertebral disc in humans only. These studies covered a wide variety of ECM features, including individual ECM components (i.e. collagens, proteoglycans, and glycoproteins), ECM architecture (i.e. collagen fibre organization and diameter), and viscoelastic properties (i.e. elastic and compressive modulus). Some ECM changes, notably calcification and the loss of collagen fibre organization, have been extensively studied across osteoarthritic tissues. However, most ECM features were only studied by one or a few papers in each tissue. When comparisons were possible, the results from animal experiments largely concurred with those from human studies, although some findings were contradictory. Conclusion. Changes in ECM composition and architecture occur throughout non-cartilage soft tissues in the osteoarthritic joint, but most of these remain poorly defined due to the low number of studies and lack of healthy comparator groups. Cite this article: Bone Joint Res 2024;13(12):703–715


Bone & Joint Research
Vol. 10, Issue 9 | Pages 558 - 570
1 Sep 2021
Li C Peng Z Zhou Y Su Y Bu P Meng X Li B Xu Y

Aims. Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. Methods. High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology. Results. More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of collagen fibres in the joint capsule. Expression of transforming growth factor beta 1 (TGF-β1) was downregulated, while that of TGF-β2, Mothers against decapentaplegic homolog 3 (SMAD3), and WNT11 were upregulated in DDH, and alpha smooth muscle actin (αSMA), a key myofibroblast marker, showed marginal increase. In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH. Conclusion. DDH is associated with the loss of collagen fibres and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further study. Cite this article: Bone Joint Res 2021;10(9):558–570


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 8 | Pages 1019 - 1024
1 Aug 2008
Cashin M Uhthoff H O’Neill M Beaulé PE

Damage to and repair of the acetabular labral-chondral complex are areas of clinical interest in the treatment of young adults with pain in the hip and in the prevention of degenerative arthritis of the hip. There are varying theories as to why most acetabular tears are located anterosuperiorly. We have studied the prenatal development of the human acetabular labral-chondral complex in 11 fetal hips, aged from eight weeks of gestation to term. There were consistent differences between the anterior and posterior acetabular labral-chondral complex throughout all ages of gestation. The anterior labrum had a somewhat marginal attachment to the acetabular cartilage with an intra-articular projection. The posterior labrum was attached and continuous with the acetabular cartilage. Anteriorly, the labral-chondral transition zone was sharp and abrupt, but posteriorly it was gradual and interdigitated. The collagen fibres of the anterior labrum were arranged parallel to the labral-chondral junction, but at the posterior labrum they were aligned perpendicular to the junction. We believe that in the anterior labrum the marginal attachment and the orientation of the collagen fibres parallel to the labral-chondral junction may render it more prone to damage than the posterior labrum in which the collagen fibres are anchored in the acetabular cartilage. The anterior intra-articular projection of the labrum should not be considered to be a pathological feature


The Journal of Bone & Joint Surgery British Volume
Vol. 51-B, Issue 3 | Pages 529 - 539
1 Aug 1969
Liverpool GM Roy S

1. The surface of mature adult human articular cartilage from the knee has been studied by electron microscopy in eleven patients ranging in age from thirty-seven to eighty-three years. The ultrastructural appearance varies from person to person and often from area to area in the same specimen. These variations range from an intact surface to one showing overt fibrillation visible with the light microscope. 2. In areas where the articular surface appears intact the underlying superficial matrix consists of closely packed collagen fibres with only a small amount of interfibrillary ground substance. The collagen fibres show a predominantly tangential orientation in this region of the cartilage. Osmophilic lipidic bodies are sometimes seen in the matrix very close to the joint surface. 3. The appearances under the electron microscope are altered in what is interpreted as an early ultrastructural change in the development of cartilage fibrillation. In the affected areas the collagen fibres show abnormally wide separation by an excessive amount of interfibrillary matrix. Collagen fibres become directly exposed to the joint cavity, and the surface can also show accumulations of finely granular material and sometimes tuft-like projections containing collagen fibres and fine fibrils. At a slightly later stage shallow clefts and steeply sloping curves are apparent at the surface. It is suggested that these various alterations precede the development of overt fibrillation visible under the light microscope. 4. Electron micrographs occasionally show small "blisters" at the articular surface. Electron microscopy has not given evidence of shedding of cells into the joint cavity from non-fibrillated areas of adult human articular cartilage. Cells can, however, sometimes become exposed at the surface in fibrillated areas


Bone & Joint Research
Vol. 9, Issue 4 | Pages 173 - 181
1 Apr 2020
Schon J Chahla J Paudel S Manandhar L Feltham T Huard J Philippon M Zhang Z

Aims. Femoroacetabular impingement (FAI) is a potential cause of hip osteoarthritis (OA). The purpose of this study was to investigate the expression profile of matrix metalloproteinases (MMPs) in the labral tissue with FAI pathology. Methods. In this study, labral tissues were collected from four FAI patients arthroscopically and from three normal hips of deceased donors. Proteins extracted from the FAI and normal labrums were separately applied for MMP array to screen the expression of seven MMPs and three tissue inhibitors of metalloproteinases (TIMPs). The expression of individual MMPs and TIMPs was quantified by densitometry and compared between the FAI and normal labral groups. The expression of selected MMPs and TIMPs was validated and localized in the labrum with immunohistochemistry. Results. On MMP arrays, most of the targeted MMPs and TIMPs were detected in the FAI and normal labral proteins. After data normalization, in comparison with the normal labral proteins, expression of MMP-1 and MMP-2 in the FAI group was increased and expression of TIMP-1 reduced. The histology of the FAI labrum showed disorderly cell distribution and altered composition of thick and thin collagen fibres. The labral cells expressing MMP-1 and MMP-2 were localized and their percentages were increased in the FAI labrum. Immunohistochemistry confirmed that the percentage of TIMP-1 positive cells was reduced in the FAI labrum. Conclusion. This study established an expression profile of MMPs and TIMPs in the FAI labrum. The increased expression of MMP-1 and MMP-2 and reduced expression of TIMP-1 in the FAI labrum are indicative of a pathogenic role of FAI in hip OA development. Cite this article:Bone Joint Res. 2020;9(4):173–181


Bone & Joint Research
Vol. 8, Issue 6 | Pages 232 - 245
1 Jun 2019
Lu C Zhang T Reisdorf RL Amadio PC An K Moran SL Gingery A Zhao C

Objectives. Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery. Methods. A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs). Results. Failed-repair stump tissue showed cellular accumulation of crumpled and disoriented collagen fibres. Compared with normal tendon, stump tissue had significantly higher gene expression of collagens I and III, matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF). The stump TDSCs presented both mesenchymal stem and haematopoietic cell markers with significantly increased expression of CD34, CD44, and CD90 markers. Stump TDSCs exhibited similar migration but a lower proliferation rate, as well as similar osteogenic differentiation but a lower chondrogenic/adipogenic differentiation capability, compared with normal TDSCs. Stump TDSCs also showed increasing levels of SRY-box 2 (Sox2), octamer-binding transcription factor 4 (Oct4), tenomodulin (TNMD), and scleraxis (Scx) protein and gene expression. Conclusion. We found that a failed repair stump had increased cellularity that preserved both mesenchymal and haematopoietic stem cell characteristics, with higher collagen synthesis, MMP, and growth factor gene expression. This study provides evidence that tendon stump tissue has regenerative potential. Cite this article: C-C. Lu, T. Zhang, R. L. Reisdorf, P. C. Amadio, K-N. An, S. L. Moran, A. Gingery, C. Zhao. Biological analysis of flexor tendon repair-failure stump tissue: A potential recycling of tissue for tendon regeneration. Bone Joint Res 2019;8:232–245. DOI: 10.1302/2046-3758.86.BJR-2018-0239.R1


Bone & Joint Research
Vol. 5, Issue 11 | Pages 577 - 585
1 Nov 2016
Hase E Sato K Yonekura D Minamikawa T Takahashi M Yasui T

Objectives. This study aimed to evaluate the histological and mechanical features of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging and tensile testing. Materials and Methods. A total of eight male Japanese white rabbits were used for this study. The flexor digitorum tendons in their right leg were sharply transected, and then were repaired by intratendinous stitching. At four weeks post-operatively, the rabbits were killed and the flexor digitorum tendons in both right and left legs were excised and used as specimens for tendon healing (n = 8) and control (n = 8), respectively. Each specimen was examined by SHG imaging, followed by tensile testing, and the results of the two testing modalities were assessed for correlation. Results. While the SHG light intensity of the healing tendon samples was significantly lower than that of the uninjured tendon samples, 2D Fourier transform SHG images showed a clear difference in collagen fibre structure between the uninjured and the healing samples, and among the healing samples. The mean intensity of the SHG image showed a moderate correlation (R. 2. = 0.37) with Young’s modulus obtained from the tensile testing. Conclusion. Our results indicate that SHG microscopy may be a potential indicator of tendon healing. Cite this article: E. Hase, K. Sato, D. Yonekura, T. Minamikawa, M. Takahashi, T. Yasui. Evaluation of the histological and mechanical features of tendon healing in a rabbit model with the use of second-harmonic-generation imaging and tensile testing. Bone Joint Res 2016;5:577–585. DOI: 10.1302/2046-3758.511.BJR-2016-0162.R1


Bone & Joint Research
Vol. 9, Issue 6 | Pages 293 - 301
1 Jun 2020
Hexter AT Hing KA Haddad FS Blunn G

Aims. To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements. Methods. A total of 12 sheep underwent unilateral single-bundle ACL reconstruction using pSFT. Two femoral fixation devices were investigated: Group 1 (n = 6) used cortical suspensory fixation (Endobutton CL) and Group 2 (n = 6) used cross-pin fixation (Stratis ST). A soft screw was used for tibial fixation. Functional recovery was quantified using force plate analysis at weeks 5, 8, and 11. The sheep were euthanized after 12 weeks and comprehensive histological analysis characterized graft healing at the graft-bone interface and the intra-articular graft (ligamentization). Results. The pSFT remodelled into a ligament-like structure and no adverse inflammatory reaction was seen. The ground reaction force in the operated leg of the Endobutton group was higher at 11 weeks (p < 0.05). An indirect insertion was seen at the graft-bone interface characterized by Sharpey-like fibres. Qualitative differences in tendon remodelling were seen between the two groups, with greater crimp-like organization and more aligned collagen fibres seen with Endobutton fixation. One graft rupture occurred in the cross-pin group, which histologically showed low collagen organization. Conclusion. Decellularized pSFT xenograft remodels into a ligament-like structure after 12 weeks and regenerates an indirect-type insertion with Sharpey-like fibres. No adverse inflammatory reaction was observed. Cortical suspensory femoral fixation was associated with more enhanced graft remodelling and earlier functional recovery when compared with the stiffer cross-pin fixation


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 9 | Pages 1245 - 1251
1 Sep 2006
Pendegrass CJ Oddy MJ Sundar S Cannon SR Goodship AE Blunn GW

We examined the mechanical properties of Vicryl (polyglactin 910) mesh in vitro and assessed its use in vivo as a novel biomaterial to attach tendon to a hydroxyapatite-coated metal implant, the interface of which was augmented with autogenous bone and marrow graft. This was compared with tendon re-attachment using a compressive clamp device in an identical animal model. Two- and four-ply sleeves of Vicryl mesh tested to failure under tension reached 5.13% and 28.35% of the normal ovine patellar tendon, respectively. Four-ply sleeves supported gait in an ovine model with 67.05% weight-bearing through the operated limb at 12 weeks, without evidence of mechanical failure. Mesh fibres were visible at six weeks but had been completely resorbed by 12 weeks, with no evidence of chronic inflammation. The tendon-implant neoenthesis was predominantly an indirect type, with tendon attached to the bone-hydroxyapatite surface by perforating collagen fibres


Bone & Joint Research
Vol. 6, Issue 4 | Pages 231 - 244
1 Apr 2017
Zhang J Yuan T Zheng N Zhou Y Hogan MV Wang JH

Objectives. After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP). Methods. Wounds created in rat ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN-PRP); PRP; or saline (control), followed by histological and immunochemical analyses, and mechanical testing of the rat ATEs after three months of healing. Results. Histological analysis showed well organised arrangement of collagen fibres and proteoglycan formation in the wounded ATEs in the KGN-PRP group. Furthermore, immunohistochemical analysis revealed fibrocartilage formation in the KGN-PRP-treated ATEs, evidenced by the presence of both collagen I and II in the healed ATE. Larger positively stained collagen III areas were found in both PRP and saline groups than those in the KGN-PRP group. Chondrocyte-related genes, SOX9 and collagen II, and tenocyte-related genes, collagen I and scleraxis (SCX), were also upregulated by KGN-PRP. Moreover, mechanical testing results showed higher ultimate tensile strength in the KGN-PRP group than in the saline control group. In contrast, PRP treatment appeared to have healed the injured ATE but induced no apparent formation of fibrocartilage. The saline-treated group showed poor healing without fibrocartilage tissue formation in the ATEs. Conclusions. Our results show that injection of KGN-PRP induces fibrocartilage formation in the wounded rat ATEs. Hence, KGN-PRP may be a clinically relevant, biological approach to regenerate injured enthesis effectively. Cite this article: J. Zhang, T. Yuan, N. Zheng, Y. Zhou, M. V. Hogan, J. H-C. Wang. The combined use of kartogenin and platelet-rich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses. Bone Joint Res 2017;6:231–244. DOI: 10.1302/2046-3758.64.BJR-2017-0268.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 4 | Pages 535 - 541
1 Apr 2008
Pendegrass CJ Sundar S Oddy MJ Cannon SR Briggs T Blunn GW

We used an in vivo model to assess the use of an autogenous cancellous bone block and marrow graft for augmenting tendon reattachment to metallic implants. We hypothesised that augmentation of the tendon-implant interface with a bone block would enable retention of the graft on the implant surface, enhance biological integration, and result in more consistent functional outcomes compared with previously reported morcellised graft augmentation techniques. A significant improvement in functional weight-bearing was observed between six and 12 weeks. The significant increase in ground reaction force through the operated limb between six and 12 weeks was greater than that reported previously with morcellised graft augmented reconstructions. Histological appearance and collagen fibre orientation with bone block augmentation more closely resembled that of an intact enthesis compared with the morcellised grafting technique. Bone block augmentation of tendon-implant interfaces results in more reliable functional and histological outcomes, with a return to pre-operative levels of weight-bearing by 24 weeks


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 2 | Pages 205 - 209
1 Feb 2012
Kadonishi Y Deie M Takata T Ochi M

We examined whether enamel matrix derivative (EMD) could improve healing of the tendon–bone interface following reconstruction of the anterior cruciate ligament (ACL) using a hamstring tendon in a rat model. ACL reconstruction was performed in both knees of 30 Sprague-Dawley rats using the flexor digitorum tendon. The effect of commercially available EMD (EMDOGAIN), a preparation of matrix proteins from developing porcine teeth, was evaluated. In the left knee joint the space around the tendon–bone interface was filled with 40 µl of EMD mixed with propylene glycol alginate (PGA). In the right knee joint PGA alone was used. The ligament reconstructions were evaluated histologically and biomechanically at four, eight and 12 weeks (n = 5 at each time point). At eight weeks, EMD had induced a significant increase in collagen fibres connecting to bone at the tendon–bone interface (p = 0.047), whereas the control group had few fibres and the tendon–bone interface was composed of cellular and vascular fibrous tissues. At both eight and 12 weeks, the mean load to failure in the treated specimens was higher than in the controls (p = 0.009). EMD improved histological tendon–bone healing at eight weeks and biomechanical healing at both eight and 12 weeks. EMD might therefore have a human application to enhance tendon–bone repair in ACL reconstruction


The Journal of Bone & Joint Surgery British Volume
Vol. 71-B, Issue 3 | Pages 509 - 513
1 May 1989
Mackie I Green M Clarke H Isaac D

Bone samples from the iliac crest of patients with no signs of bone disorder were treated with collagenase to remove the collagen component and so allow detailed observation of the mineral hydroxyapatite. Both polished and unpolished surfaces were studied in the scanning electron microscope and they showed that the mineral component of bone is composed of small rounded units about 10 nm across which are fused together to form larger spheroidal units roughly 100 nm in diameter. In the unpolished surfaces these 100 nm units are seen to aggregate to form columns approximately parallel to their neighbours and with numerous interconnections forming a continuous mineral phase. The polished sections also show the hydroxyapatite as a continuous phase of contiguous spheroids and the holes from which the collagen fibres were removed are clearly revealed. Lamellations in the surface are interpreted as resulting from adjacent layers of collagen fibres having orientations approximately perpendicular to each other


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 12 | Pages 1632 - 1637
1 Dec 2009
Sonnabend DH Young AA

While the evolution of the bony skeleton of the shoulder girdle is well described, there is little information regarding the soft tissues, in particular of the rotator cuff. We dissected the shoulders of 23 different species and compared the anatomical features of the tendons of the rotator cuff. The alignment and orientation of the collagen fibres of some of the tendons were also examined histologically. The behaviour of the relevant species was studied, with particular reference to the extent and frequency of forward-reaching and overhead activity of the forelimb. In quadrupedal species, the tendons of supraspinatus, infraspinatus and teres minor were seen to insert into the greater tuberosity of the humerus separately. They therefore did not form a true rotator cuff with blending of the tendons. This was only found in advanced primates and in one unusual species, the tree kangaroo. These findings support the suggestion that the appearance of the rotator cuff in the evolutionary process parallels anatomical adaptation to regular overhead activity and the increased use of the arm away from the sagittal plane


The Journal of Bone & Joint Surgery British Volume
Vol. 48-B, Issue 4 | Pages 804 - 825
1 Nov 1966
Baker SL Dent CE Friedman M Watson L

1. A clinical, radiological and histological description of a patient with fibrogenesis imperfecta ossium is given. We think that this is the first case in which diagnosis has been made during the life of the patient. 2. The disease is characterised by a defect in the formation of the collagen fibres of the bone matrix. There is also a failure of normal calcification of the matrix, giving rise to the appearance of wide "osteoid" seams. When examined with the polarising microscope and when stained with Gomori's reticulin stain the collagen fibres can be seen to be grossly deficient and abnormal. 3. The patient presented at the age of fifty-four years with bone pain and multiple fractures. The only biochemical abnormality detected in the plasma was an elevated alkaline phosphatase. He was also in negative calcium balance. 4. Treatment with vitamin D. 2. , later changed to dihydrotachysterol, appears to have produced clinical, biochemical and radiological improvement. It appears that a direct action of the vitamin on the abnormal bone collagen must be postulated, in addition to its known actions on the calcifying mechanisms. 5. An unusual feature of the case was the slow development of a total unresponsiveness to large doses of vitamin D. 2. , in spite of a markedly elevated level of vitamin D in the plasma. There was later a response to a much smaller dose of dihydrotachysterol, which is being maintained to date


The Journal of Bone & Joint Surgery British Volume
Vol. 38-B, Issue 1 | Pages 378 - 417
1 Feb 1956
Baker SL

1. A description is given of the pathology of a generalised skeletal disease characterised by a defect in the formation of the collagen fibres of the bone matrix—"fibrogenesis imperfecta ossium.". 2. Material from two cases, a woman of fifty-six and a man of sixty-four, was examined. All the samples of bone from both patients showed the same defect, which was severe in most of the specimens, and there was radiographic evidence of similar widespread bone changes in both cases. 3. The defect is clear-cut and striking histologically, provided that sections are examined with a polarising microscope, and/or by reticulin methods. 4. As a result of the defect in the bone matrix this fails to calcify, or calcifies imperfectly, showing wide osteoid borders as in severe osteomalacia. But the fibre defect separates it quite clearly from osteomalacia, in which the fibre structure of the osteoid tissue is normal. Moreover neither the biochemical findings (Case 2) nor the radiographic appearances correspond with those of osteomalacia. 5. The collagen fibre defect is confined to the bone matrix; no defect was found in the soft tissue collagen, and even the periosteum shows a normal fibre structure. 6. Both the clinical and the histological evidence indicate that the disease is not congenital, but was, in these two patients, apparently acquired during middle age. There was no family history of bone disease. 7. The cause of the condition is quite obscure. It is not inflammatory or neoplastic, nor is there histological or clinical evidence of a toxic origin. If it is a deficiency disease it is unlike any known vitamin or other chemical deficiency


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 9 | Pages 1257 - 1262
1 Sep 2009
Sundar S Pendegrass CJ Oddy MJ Blunn GW

We used demineralised bone matrix (DBM) to augment re-attachment of tendon to a metal prosthesis in an in vivo ovine model of reconstruction of the extensor mechanism at the knee. We hypothesised that augmentation of the tendon-implant interface with DBM would enhance the functional and histological outcomes as compared with previously reported control reconstructions without DBM. Function was assessed at six and 12 weeks postoperatively, and histological examination was undertaken at 12 weeks. A significant increase of 23.5% was observed in functional weight-bearing at six weeks in the DBM-augmented group compared with non-augmented controls (p = 0.004). By 12 weeks augmentation with DBM resulted in regeneration of a more direct-type enthesis, with regions of fibrocartilage, mineralised fibrocartilage and bone. In the controls the interface was predominantly indirect, with the tendon attached to the bone graft-hydroxyapatite base plate by perforating collagen fibres


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 3 | Pages 406 - 413
1 May 1999
McMahon PJ Dettling J Sandusky MD Tibone JE Lee TQ

Surgical treatment for traumatic, anterior glenohumeral instability requires repair of the anterior band of the inferior glenohumeral ligament, usually at the site of glenoid insertion, often combined with capsuloligamentous plication. In this study, we determined the mechanical properties of this ligament and the precise anatomy of its insertion into the glenoid in fresh-frozen glenohumeral joints of cadavers. Strength was measured by tensile testing of the glenoid-soft-tissue-humerus (G-ST-H) complex. Two other specimens of the complex were frozen in the position of apprehension, serially sectioned perpendicular to the plane containing the anterior and posterior rims of the glenoid, and stained with Toluidine Blue. On tensile testing, eight G-ST-H complexes failed at the site of the glenoid insertion, representing a Bankart lesion, two at the insertion into the humerus, and two at the midsubstance. For those which failed at the glenoid attachment the mean yield load was 491.0 N and the mean ultimate load, 585.0 N. At the glenoid region, stress at yield was 7.8 ± 1.3 MPa and stress at failure, 9.2 ± 1.5 MPa. The permanent deformation, defined as the difference between yield and ultimate deformation, was only 2.3 ± 0.8 mm. The strain at yield was 13.0 ± 0.7% and at failure, 15.4 ± 1.2%; therefore permanent strain was only 2.4 ± 1.1%. Histological examination showed that there were two attachments of the anterior band of the inferior glenohumeral ligament at the site of the glenoid insertion. In one, poorly organised collagen fibres inserted into the labrum. In the other, dense collagen fibres were attached to the front of the neck of the glenoid


The Journal of Bone & Joint Surgery British Volume
Vol. 40-B, Issue 4 | Pages 742 - 764
1 Nov 1958
Allbrook D Kirkaldy-Willis WH

The experiments were performed to answer three main questions. These and our answers may be summarised as follows. What is the precise mechanism of healing of a raw bony surface in a joint? What cells are involved? Where do they originate?—In all the implant experiments and in the control series the fundamental mechanism of healing was similar. 1. A massive proliferation of fibroblasts occurred from the cut periosteum, from the cut joint capsule, and to a lesser extent from the medullary canal. 2. Fibroblasts grew centripetally in the first few weeks after operation, attempting to form a "fibroblast cap" to the cut bone end. 3. Fibroblasts of this cap near the cut bone spicules metamorphosed to become prechondroblasts, chondroblasts laying down cartilage matrix, and hypertrophied (alkaline phosphatase-secreting) chondrocytes lying in a calcified matrix. 4. This calcified cartilage matrix was invaded by dilated capillaries probably bearing osteoblasts which laid down perivascular (endochondral) bone. 5. Some of the cells of projecting bone spicules died and their matrix was eroded in the presence of many osteoclasts. 6. In the control experiments of simple excision of the radial head new bone was produced at the periphery only by processes (3) and (4). This sealed off the underlying peripheral cortical bone from the superficially placed peripheral articular surface of fibrocartilage. At about a year from operation the central portion of the articular surface was still formed of bare bone, or of bone spicules covered by a thin layer of irregularly arranged collagen fibres. The opposite capitular articular cartilage was badly eroded. Does the introduction of a dead cartilage implant over the raw bone end affect in any way the final constitution of the new articular surface?—In the implant experiments the new bone produced by processes (3) and (4) formed, after about a year, a complete cortical plate which entirely sealed off the cut end of the radius and left a superficially placed articular covering of smooth fibrocartilage, closely resembling a normal joint surface. The opposite capitular articular surface was normal. What is the final fate of such an implant?—Whale cartilage implants underwent replacement by fibroblasts and collagen fibres, and took about nine months to disappear. The cartilage of fixed autotransplants and homotransplants underwent similar gradual replacement, and took about the same time in each case. The dead bone, implanted in association with the cartilage in both cases, acted as a nidus for hyaline cartilage production by chondrocytes derived from fibroblasts. This cartilage underwent endochondral ossification. This observation suggests that induction by non-cellular osseous material is a factor in chondrification and ossification. All the implants functioned as temporary articular menisci or in some cases as temporary radial articular surfaces. They were always replaced by a permanent fibrocartilaginous meniscus, or a fibrocartilaginous articular surface. An implant did, in fact, always act as a temporary protecting cap and mould for the subjacent growth offibroblasts which was necessary for the production of a satisfactory new joint surface


The Journal of Bone & Joint Surgery British Volume
Vol. 52-B, Issue 3 | Pages 564 - 570
1 Aug 1970
Bullough PG Munuera L Murphy J Weinstein AM

1. The orientation of collagen fibres of the menisci of the knee has been demonstrated by polarised light microscopy. 2. As might be supposed from its fibre structure, the ultimate tensile strength of the meniscal tissue is dependent upon the axis of loading. 3. The tensile strength of the meniscus is similar to that of articular cartilage


The Journal of Bone & Joint Surgery British Volume
Vol. 40-B, Issue 3 | Pages 552 - 557
1 Aug 1958
Horton WG

By polarising microscope and x-ray crystallographic techniques the annulus fibrosus has been shown to consist of regularly oriented sheets of collagen fibres. These results have been interpreted in terms of an elastic mechanism whereby thrust from the nucleus causes increased girth in the annulus. It is suggested that this is accomplished by a change in the angle between the axis of the fibres in adjacent uniaxial layers of the annulus. Furthermore, the loss of elasticity of the intervertebral disc associated with age would seem to be mainly due to changes occurring in the nucleus pulposus


The Journal of Bone & Joint Surgery British Volume
Vol. 60-B, Issue 2 | Pages 228 - 233
1 May 1978
Psaila J Mansel R

The surface ultrastructure of ganglia has been studied using the scanning electron microscope. This study showed that the ganglion wall consists of multidirectional strata of collagen fibres and has no cellular lining. The wall has a sponge-like appearance and does not appear degenerate or necrotic. Comparison with synovial membrane and adventitious bursa confirmed that these are distinct structures which have a cellular lining. Ganglia probably arise from the multifunctional mesenchymal cells which are found within their walls. The ganglion fluid may also originate from these cells


The Journal of Bone & Joint Surgery British Volume
Vol. 33-B, Issue 2 | Pages 251 - 257
1 May 1951
MacConaill MA

1. All articulating cartilages are fibrocartilages. 2. The articular cartilages of the synovial joints are largely composed of collagen fibres. 3. These fibres form a dense network, the fibres of which run obliquely between the articular surface and the bone. 4. This network is operative when the parts are at rest and in contact under pressure. It takes the tensile component of the resultant shear stress, and is a postural mechanism of the joint. 5. The articular cartilage is most heavily chondrified at its centre, between the juxta-synovial and juxta-osseous parts. 6. The technique for demonstrating the fibrous structure is described


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 6 | Pages 991 - 994
1 Nov 1999
Morgan-Jones RL Cross MJ

Thirty cruciate ligaments were retrieved from either cadavers or limbs which had been amputated. Each specimen was sectioned and stained to demonstrate the presence of collagen, nerves and vessels. All 30 specimens contained an interconnecting band of collagen fibres between the anterior and posterior cruciate ligaments. Vascular structures were present in all specimens and nerve fibres were identified in 26 (86%). We have called this structure the ‘intercruciate band’. The anterior and posterior cruciate ligaments should no longer be thought of in isolation, but together as a ‘cruciate complex’


The Journal of Bone & Joint Surgery British Volume
Vol. 67-B, Issue 4 | Pages 645 - 649
1 Aug 1985
Mendes D Angel D Grishkan A Boss J

The soft tissue response to carbon fibre was studied histologically one and a half years after being used to reconstruct the lateral collateral ligament of the human knee. A remarkably consistent pattern was seen in the induced ligament. The basic pattern was a "composite unit", consisting of a core of carbon fibre enveloped in a concentric manner by coherent layers of fibroblasts and collagen fibres. This new structure seemed to have been induced by continuous irritation caused by the physical structure of the carbon fibres; it is unlikely ever to acquire the structure of a natural ligament. However, it is biologically compatible and is biomechanically sufficient as long as the entire tow of carbon fibres is preserved


The Journal of Bone & Joint Surgery British Volume
Vol. 42-B, Issue 3 | Pages 588 - 605
1 Aug 1960
Smith JW

1. The arrangement of collagen fibres in the secondary osteones in human femora and tibiae has been examined. The fibres were observed in paraffin sections stained by Weidenreich's method. 2. Three fibre patterns have been observed. They differ from one another in the relative numbers of longitudinal and circumferential fibres which they contain, and in the degree of lamellation which they exhibit. 3. The incidence of the three fibre patterns has been correlated with the relative ages of the regions of bone in which they occur. 4. The possibility of a correlation between variations in fibre pattern and certain recent microradiographic observations is discussed


The Journal of Bone & Joint Surgery British Volume
Vol. 55-B, Issue 3 | Pages 581 - 587
1 Aug 1973
Lothe K Spycher MA Rüttner JR

1. Human articular cartilage from normal femoral heads and from cases of osteoarthrosis in subjects of various ages has been examined histologically and by electron microscopy. 2. In specimens from middle-aged and old subjects, peculiar "matrix-streaks" have been observed in the deep zone of the pressure areas as oblique bands extending from the pericellubar halos into the adjacent matrix. 3. Ultrastructurally the streaks are correlated with an undulating pattern of the radially oriented collagen fibres. 4. The streaks are considered to result from a focal lack of acid mucopolysaccharide and from natural forces on the articular cartilage. Their appearance is assumed to be an early sign of cartilage disintegration associated with ageing


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 1 | Pages 39 - 44
1 Jan 1992
Shearer Roach H Parsons S

We describe the histology of a specimen taken from an amputated leg seven months after a 15 cm bone gap in the tibia had been closed by bone transport. Lengthening appeared to have occurred by repeated minor trauma to the bone, with the fractured trabeculae in sufficiently close contact for the repair process to proceed. Osteogenesis did not occur through a cartilage phase, but the fracture gaps were bridged by collagen fibres, around which new bone formed. Microfractures had repaired by primary healing with woven bone and with no microcallus. Small regions of bone were necrotic. Resorption of the necrotic bone and remodelling of the immature bundle and woven bone were still at an early stage, suggesting that complete remodelling in man may take years rather than months


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 3 | Pages 450 - 456
1 Apr 2000
Azangwe G Mathias KJ Marshall D

In a study combining tissue mechanics and fracture morphology for the first time, we examined the ruptured surfaces of anterior cruciate ligaments of rabbits and related their appearance to the initial loading conditions. Sixteen specimens were stretched to failure at rates of displacement of 10 and 500 mm/min. We used video images to study the changes which occurred during the fracture process and SEM to examine the appearance of the ruptured surfaces. The surfaces of ligaments tested at 10 mm/min had more pulled-out collagen fibres and the fibres had more pronounced waviness compared with those tested at 500 mm/min. We have shown that the macroscopic appearance of ruptured ligaments can be related to their microscopic appearance and that it is possible to deduce whether failure was by gradual tearing of the fibres or catastrophic failure


The Journal of Bone & Joint Surgery British Volume
Vol. 76-B, Issue 3 | Pages 450 - 457
1 May 1994
Fukuhara K Schollmeier G Uhthoff H

We studied 16 club feet and 27 normal feet from spontaneously aborted human fetuses in the second trimester of gestation and measured the length of the spring ligament, and the declination angle and size of the talus. We also studied the cellular characteristics of the spring ligament and the immunohistochemical features of the medial ankle ligaments using monoclonal antibodies against type-III collagen, desmin, vimentin, and smooth muscle actin. Histomorphometric results indicated that the talar deformity was not the primary lesion. Histological and immunohistochemical findings showed that the cells and collagen fibres of the medial ankle ligaments of club feet appeared to be the site of the earliest changes, in that they had lost their spatial orientation and had contracted. In severe club feet before the third trimester of gestation, myofibroblast-like cells seemed to create a disorder of the ligaments resembling fibromatosis. This led to contraction and resulted in typical club-foot deformity


The Journal of Bone & Joint Surgery British Volume
Vol. 40-B, Issue 3 | Pages 558 - 573
1 Aug 1958
Storey E

1. When cortisone is administered to rabbits there is early rapid resorption of bone and a partial inhibition of new bone formation. After a few days the effect becomes less obvious, so that, if observations are made at later stages, the results may be ascribed then to simple inhibition of bone growth. 2. The effect of mechanical stress has been studied in the jaw. When tooth movement is induced mechanically there is, in ordinary circumstances, a resorption of bone on the side to which the tooth is moving (the "pressure" side) and bone formation on the opposite side (the "tension" side). After administration of cortisone there is increased resorption on the "pressure" side and there is greater resorption of connective tissues here. On the "tension" side there is resorption and inhibition of bone formation. 3. In the areas of stress, when cortisone is administered, collagen fibres are no longer in apposition, being separated by spaces presumably filled with altered ground substance; this kind of change may be responsible for many of the observed phenomena. 4. A.C.T.H. does not produce a demonstrable resorptive effect on bone or connective tissue until it has been administered for periods longer than is required for cortisone (three weeks); even then the change is not pronounced. 5. In the guinea pig there is slight delay in bone formation with large doses of both cortisone and A.C.T.H., but no significant bone resorption occurs


The Journal of Bone & Joint Surgery British Volume
Vol. 44-B, Issue 1 | Pages 165 - 193
1 Feb 1962
Makin M

1. In the experiments undertaken autogenous vesical mucosal transplants were made in guinea-pigs. The transplanted mucosa proliferates and forms a nodule. Central necrosis of the nodule and the secretion of the proliferating epithelium combine to form a cyst filled with a viscous fluid. 2. Before the cyst is well defined some of this fluid diffuses into the sub-epithelial connective tissue, producing areas of tissue oedema which later are transformed into translucent hyaloid islands. With further condensation of the collagen fibres, these areas are converted into primitive bone. The hyaloid islands act as a bone precursor. Bone always formed in the wall of the cyst within thirty days except in cases of sepsis or death of the transplant, when there was no osteogenesis. Homografts of vesical mucosa were found unreliable in their capacity to induce bone. 3. The results of the histochemical investigation and radiographic diffraction of the hyaloid areas suggest that the proliferating mucosa is the source of the inducing agent. 4. Bone can be induced only in sites where a primitive vascular connective tissue is growing and where there exists an adequate blood supply. 5. The rapid rate of osteogenesis can be seen in the radiographs of induced bone in radial defects. The electron-microscopic study of the induced bone at three weeks confirmed that osteoid had been formed so quickly that calcification had not yet taken place. 6. The relationship between the bone induced by transplanting vesical epithelium and the formation of urinary calculi is discussed and their common origin postulated


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 5 | Pages 918 - 923
1 Sep 1998
Bruns J Kahrs J Kampen J Behrens P Plitz W

Our aim was to examine the potential of autologous perichondral tissue to form a meniscal replacement. In 18 mature sheep we performed a complete medial meniscectomy. The animals were then divided into two groups: 12 had a meniscal replacement using strips of autologous perichondral tissue explanted from the lower rib (group G) and six (group C) served as a control group without a meniscal replacement. In all animals restriction from weight-bearing was achieved by means of transection and partial resection of tendo Achillis. Six animals (four from group G and two from group C) were each killed at 3, 6 and 12 months. The grafts and the underlying articular cartilage were removed and studied by gross macroscopic examination, light microscopy, SEM, polarised light examination, and by biomechanical tests. In all the transplanted animals a new perichondral meniscus developed. After three months the transplants resembled normal menisci in size and thickness, while in the control animals only small rims of spontaneously grown tissue were seen. Microscopically, the perichondral menisci showed a normal orientation of collagen fibres and normal cellular characteristics, but in the central region, areas of calcification disturbed the regular tissue differentiation. Healing tissue in control animals lacked the normal fibre orientation and cellularity. SEM of perichondral menisci showed surface characteristics similar to those of normal sheep menisci without fissures and lacerations; the control specimens had these defects. The femoral and tibial cartilage in contact with the new menisci had normal surface characteristics apart from one animal with slight surface irregularities. Control animals showed superficial lesions after three months which increased at six to 12 months postoperatively. Microangiography of the newly grown tissue demonstrated a less intense vascularisation after three months when compared with normal menisci. The failure stress and tensile modulus of perichondral menisci were significantly lower than those of normal contralateral menisci, and spontaneously regenerated tissue in meniscectomised animals had even lower values. There were no significant differences in values between newly grown perichondral menisci and spontaneously grown tissue


Bone & Joint Research
Vol. 12, Issue 5 | Pages 339 - 351
23 May 2023
Tan J Liu X Zhou M Wang F Ma L Tang H He G Kang X Bian X Tang K

Aims

Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing.

Methods

A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 342 - 352
9 Jul 2024
Cheng J Jhan S Chen P Hsu S Wang C Moya D Wu Y Huang C Chou W Wu K

Aims

To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration.

Methods

The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens.


Bone & Joint Open
Vol. 4, Issue 8 | Pages 628 - 635
22 Aug 2023
Hedlundh U Karlsson J Sernert N Haag L Movin T Papadogiannakis N Kartus J

Aims

A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach.

Methods

A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 667 - 676
19 Oct 2023
Forteza-Genestra MA Antich-Rosselló M Ramis-Munar G Calvo J Gayà A Monjo M Ramis JM

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

Methods

pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods

The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 880 - 887
1 Aug 2023
Onodera T Momma D Matsuoka M Kondo E Suzuki K Inoue M Higano M Iwasaki N

Aims

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury.

Methods

A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 561 - 574
10 Aug 2022
Schulze-Tanzil GG Delgado Cáceres M Stange R Wildemann B Docheva D

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

Methods

We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims

Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods

Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 474 - 484
10 Sep 2024
Liu Y Li X Jiang L Ma J

Aims

Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

Methods

Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


Bone & Joint Research
Vol. 11, Issue 6 | Pages 349 - 361
9 Jun 2022
Jun Z Yuping W Yanran H Ziming L Yuwan L Xizhong Z Zhilin W Xiaoji L

Aims

The purpose of this study was to explore a simple and effective method of preparing human acellular amniotic membrane (HAAM) scaffolds, and explore the effect of HAAM scaffolds with juvenile cartilage fragments (JCFs) on osteochondral defects.

Methods

HAAM scaffolds were constructed via trypsinization from fresh human amniotic membrane (HAM). The characteristics of the HAAM scaffolds were evaluated by haematoxylin and eosin (H&E) staining, picrosirius red staining, type II collagen immunostaining, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Human amniotic mesenchymal stem cells (hAMSCs) were isolated, and stemness was verified by multilineage differentiation. Then, third-generation (P3) hAMSCs were seeded on the HAAM scaffolds, and phalloidin staining and SEM were used to detect the growth of hAMSCs on the HAAM scaffolds. Osteochondral defects (diameter: 3.5 mm; depth: 3 mm) were created in the right patellar grooves of 20 New Zealand White rabbits. The rabbits were randomly divided into four groups: the control group (n = 5), the HAAM scaffolds group (n = 5), the JCFs group (n = 5), and the HAAM + JCFs group (n = 5). Macroscopic and histological assessments of the regenerated tissue were evaluated to validate the treatment results at 12 weeks.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 179 - 188
7 Mar 2023
Itoh M Itou J Imai S Okazaki K Iwasaki K

Aims

Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery.

Methods

Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers’ websites.


Bone & Joint 360
Vol. 12, Issue 5 | Pages 24 - 26
1 Oct 2023

The October 2023 Foot & Ankle Roundup360 looks at: Risk factors for failure of total ankle arthroplasties; Effects of synovial fluid fracture haematoma to tissue-engineered cartilage; Coronal plane deformity in CMT-cavovarus feet using automated 3D measurements; Immediate weightbearing after ankle fracture fixation – is it safe?; Unlocking the mystery of Mueller-Weiss disease; Diabetic foot management: predictors of failure.


The Bone & Joint Journal
Vol. 105-B, Issue 1 | Pages 5 - 10
1 Jan 2023
Crowe CS Kakar S

Injury to the triangular fibrocartilage complex (TFCC) may result in ulnar wrist pain with or without instability. One component of the TFCC, the radioulnar ligaments, serve as the primary soft-tissue stabilizer of the distal radioulnar joint (DRUJ). Tears or avulsions of its proximal, foveal attachment are thought to be associated with instability of the DRUJ, most noticed during loaded pronosupination. In the absence of detectable instability, injury of the foveal insertion of the radioulnar ligaments may be overlooked. While advanced imaging techniques such as MRI and radiocarpal arthroscopy are well-suited for diagnosing central and distal TFCC tears, partial and complete foveal tears without instability may be missed without a high degree of suspicion. While technically challenging, DRUJ arthroscopy provides the most accurate method of detecting foveal abnormalities. In this annotation the spectrum of foveal injuries is discussed and a modified classification scheme is proposed.

Cite this article: Bone Joint J 2023;105-B(1):5–10.


Bone & Joint Research
Vol. 10, Issue 2 | Pages 137 - 148
1 Feb 2021
Lawrence EA Aggleton J van Loon J Godivier J Harniman R Pei J Nowlan N Hammond C

Aims

Vertebrates have adapted to life on Earth and its constant gravitational field, which exerts load on the body and influences the structure and function of tissues. While the effects of microgravity on muscle and bone homeostasis are well described, with sarcopenia and osteoporosis observed in astronauts returning from space, the effects of shorter exposures to increased gravitational fields are less well characterized. We aimed to test how hypergravity affects early cartilage and skeletal development in a zebrafish model.

Methods

We exposed zebrafish to 3 g and 6 g hypergravity from three to five days post-fertilization, when key events in jaw cartilage morphogenesis occur. Following this exposure, we performed immunostaining along with a range of histological stains and transmission electron microscopy (TEM) to examine cartilage morphology and structure, atomic force microscopy (AFM) and nanoindentation experiments to investigate the cartilage material properties, and finite element modelling to map the pattern of strain and stress in the skeletal rudiments.


The Bone & Joint Journal
Vol. 105-B, Issue 2 | Pages 198 - 208
1 Feb 2023
Cheok T Smith T Wills K Jennings MP Rawat J Foster B

Aims

We investigated the prevalence of late developmental dysplasia of the hip (DDH), abduction bracing treatment, and surgical procedures performed following the implementation of universal ultrasound screening versus selective ultrasound screening programmes.

Methods

A systematic search of PubMed, Embase, The Cochrane Library, OrthoSearch, and Web of Science from the date of inception of each database until 27 March 2022 was performed. The primary outcome of interest was the prevalence of late detection of DDH, diagnosed after three months. Secondary outcomes of interest were the prevalence of abduction bracing treatment and surgical procedures performed in childhood for dysplasia. Only studies describing the primary outcome of interest were included.