We have examined the process of fusion of the intertransverse processes and bone graft in the rabbit by in situ hybridisation and evaluated the spatial and temporal expression of genes encoding pro-α1 (I) collagen (COL1A1), pro-α1 (II) collagen (COL2A1) and pro-α1 (X) collagen (COL10A1). Beginning at two weeks after operation, osteogenesis and chondrogenesis occurred around the transverse process and the grafted bone at the central portion of the area of the fusion mass. Osteoblasts and osteocytes at the newly-formed woven bone expressed COL1A1. At the cartilage, most chondrocytes expressed COL2A1 and some hypertrophic chondrocytes COL10A1. In some regions, co-expression of COL1A1 and COL2A1 was observed. At four weeks, such expressions for COL1A1, COL2A1 and COL10A1 became prominent at the area of the fusion mass. From four to six weeks, bone remodelling progressed from the area of the transverse processes towards the central zone. Osteoblasts lining the trabeculae expressed a strong signal for COL1A1. At the central portion of the area of the fusion mass, endochondral ossification progressed and chondrocytes expressed COL2A1 and COL10A1. Our findings show that the fusion process begins with the synthesis of collagens around the transverse processes and around the grafted bone independently. Various spatial and temporal osteogenic and chondrogenic responses, including intramembranous, endochondral and transchondroid bone formation, progress after bone grafting at the intertransverse processes. Bone formation through cartilage may play an important role in posterolateral spinal fusion

We undertook a comparative study of magnetic resonance imaging (MRI) vertebral morphometry of thoracic vertebrae of girls with adolescent idiopathic thoracic scoliosis (AIS) and age and gender-matched normal subjects, in order to investigate abnormal differential growth of the anterior and posterior elements of the thoracic vertebrae in patients with scoliosis. Previous studies have suggested that disproportionate growth of the anterior and posterior columns may contribute to the development of AIS. Whole spine MRI was undertaken on 83 girls with AIS between the age of 12 and 14 years, and Cobb’s angles of between 20° and 90°, and 22 age-matched controls. Multiple measurements of each thoracic vertebra were obtained from the best sagittal and axial MRI cuts. Compared with the controls, the scoliotic spines had longer vertebral bodies between T1 and T12 in the anterior column and shorter pedicles with a larger interpedicular distance in the posterior column. The differential growth between the anterior and the posterior elements of each thoracic vertebra in the patients with AIS was significantly different from that in the controls (p < 0.01). There was also a significant positive correlation between the scoliosis severity score and the ratio of differential growth between the anterior and posterior columns for each thoracic vertebra (p < 0.01). Compared with age-matched controls, the longitudinal growth of the vertebral bodies in patients with AIS is disproportionate and faster and mainly occurs by endochondral ossification. In contrast, the circumferential growth by membranous ossification is slower in both the vertebral bodies and pedicles

1. The methods by which epiphyses receive their blood supply was studied by means of India ink injections in monkeys. Two types were identified depending upon whether the epiphysis was entirely or partly covered by articular cartilage. In the former, nutrient vessels enter the epiphysis by traversing the perichondrium at the periphery of the plate. In the latter they enter the epiphysis by penetrating the cortex at the side of the epiphysis at a point remote from the epiphysial plate. 2. The histological changes after separation of the second type of epiphysis were also studied. After temporary interference with endochondral ossification marked by increased thickness of the epiphysial plate, healing occurred so rapidly that within three weeks it was difficult to determine that the epiphysis had been separated at all. 3. It is concluded that when nutrient vessels enter an epiphysis at a point remote from the epiphysial plate, that epiphysis can be separated without serious disturbance to its blood supply and accordingly without interference with its capacity for growth. As it has been established that an epiphysis which is entirely covered by articular cartilage cannot be separated without destruction of its blood supply and subsequent avascular necrosis (Harris and Hobson 1956), it is concluded that the prognosis of an epiphysial separation is dependent upon the degree of damage to its blood supply rather than the mechanical disturbance of the epiphysial plate

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.

1. Autografts, isografts and homografts of fibrocartilaginous callus were observed in the anterior chamber of the eye in rats. Proliferation of cartilage ceased, endochondral ossification followed, and the end-product was a new and complete ossicle with a cortex and a marrow cavity. The size and shape of the ossicle was determined by the size and shape of the sample of callus. Thus the callus in the eye performed the function of a cartilage model like that of the developing epiphysis or a healing fracture of a long bone. 2. Fibrocartilaginous callus, heavily labelled with . 3. H-thymidine, was transplanted to the eye twenty-four hours after the last injection, when there was little if any radioactive thymidine circulating in the blood. A few small chondrocytes with labelled nuclei persisted in the cores of new bone trabeculae, but the largest part of the labelled callus was resorbed and replaced by unlabelled new bone. 3. Homografts of labelled callus produced the same results as autografts at twenty-five days, but between twenty-five and forty-five days the donor cells were destroyed by the immune response of the host. 4. Isogenous transplants in host rats treated with . 3. H-thymidine between nine and thirteen days, when the callus was invaded by new blood vessels, produced many osteogenetic cells with labelled nuclei and made it possible to trace the origin of the new bone. The label appeared in the progenitor cells within twenty-four hours. While remaining thereafter in progenitor cells, it appeared also in osteoclasts (or chondroclasts) and osteoblasts in forty-eight to seventy-two hours, and in osteocytes in ninety-six to 120 hours. Chondrocytes did not proliferate and were not labelled in the eye. 5. Homogenous transplants in host rats treated with . 3. H-thymidine between five and one days before the operation also produced new bone, but contained no labelled osteoprogenitor or bone cells after twenty-five days in the eye. At forty-five days the donor tissue had been destroyed by the immune response of the host. 6. Devitalised callus was encapsulated in inflammatory connective tissue and scar. When the dead callus was absorbed by the capillaries of the host new bone formation by induction produced a scanty deposit as a delayed event in a few instances. 7. Irrespective of whether it originated in the donor or the host, a connective-tissue cell type that proliferated rapidly and became labelled with . 3. H-thymidine was identified as a progenitor cell. Differentiation and specialisation as osteoprogenitor cells occurred after the growth of blood vessels into the interior of the callus, and developed inside of excavation chambers in cartilage. Except that the interaction of the donor tissue and host cells leading to new bone formation by induction takes place in the interior of the excavation chamber, the biophysico-chemical mechanism is unknown

Aims

The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies.

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 August 2024 Oncology Roundup³⁶⁰ looks at: What factors are associated with osteoarthritis after cementation for benign aggressive bone tumour of the knee joint: a systematic review and meta-analysis; Recycled bone grafts treated with extracorporeal irradiation or liquid nitrogen freezing after malignant tumour resection; Intercalary resection of the tibia for primary bone tumours: are vascularized fibula autografts with or without allografts a durable reconstruction?; 3D-printed modular prostheses for the reconstruction of intercalary bone defects after joint-sparing limb salvage surgery for femoral diaphyseal tumours; Factors influencing the outcome of patients with primary Ewing’s sarcoma of the sacrum; The significance of surveillance imaging in children with Ewing’s sarcoma and osteosarcoma; Resection margin and soft-tissue sarcomas of the extremities treated with limb-sparing surgery and postoperative radiotherapy.

Aims

Heterotopic ossification (HO) is a common complication after elbow trauma and can cause severe upper limb disability. Although multiple prognostic factors have been reported to be associated with the development of post-traumatic HO, no model has yet been able to combine these predictors more succinctly to convey prognostic information and medical measures to patients. Therefore, this study aimed to identify prognostic factors leading to the formation of HO after surgery for elbow trauma, and to establish and validate a nomogram to predict the probability of HO formation in such particular injuries.

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases.

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.

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Aims

Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2^-/-) display accelerated bone growth.

Aims

Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy.

Adolescent idiopathic scoliosis (AIS), defined by an age at presentation of 11 to 18 years, has a prevalence of 0.47% and accounts for approximately 90% of all cases of idiopathic scoliosis. Despite decades of research, the exact aetiology of AIS remains unknown. It is becoming evident that it is the result of a complex interplay of genetic, internal, and environmental factors. It has been hypothesized that genetic variants act as the initial trigger that allow epigenetic factors to propagate AIS, which could also explain the wide phenotypic variation in the presentation of the disorder. A better understanding of the underlying aetiological mechanisms could help to establish the diagnosis earlier and allow a more accurate prediction of deformity progression. This, in turn, would prompt imaging and therapeutic intervention at the appropriate time, thereby achieving the best clinical outcome for this group of patients.

Cite this article: Bone Joint J 2022;104-B(8):915–921.

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

Aims

Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood.