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Bone & Joint Research
Vol. 9, Issue 1 | Pages 36 - 48
1 Jan 2020
González-Chávez SA Pacheco-Tena C Quiñonez-Flores CM Espino-Solis GP Burrola-De Anda JI Muñoz-Morales PM

Aims. To assess the effect of physical exercise (PE) on the histological and transcriptional characteristics of proteoglycan-induced arthritis (PGIA) in BALB/c mice. Methods. Following PGIA, mice were subjected to treadmill PE for ten weeks. The tarsal joints were used for histological and genetic analysis through microarray technology. The genes differentially expressed by PE in the arthritic mice were obtained from the microarray experiments. Bioinformatic analysis in the DAVID, STRING, and Cytoscape bioinformatic resources allowed the association of these genes in biological processes and signalling pathways. Results. Arthritic mice improved their physical fitness by 42.5% after PE intervention; it induced the differential expression of 2,554 genes. The bioinformatic analysis showed that the downregulated genes (n = 1,371) were significantly associated with cellular processes that mediate the inflammation, including Janus kinase-signal transducer and activator of transcription proteins (JAK-STAT), Notch, and cytokine receptor interaction signalling pathways. Moreover, the protein interaction network showed that the downregulated inflammatory mediators interleukin (IL) 4, IL5, IL2 receptor alpha (IL2rα), IL2 receptor beta (IL2rβ), chemokine ligand (CXCL) 9, and CXCL12 were interacting in several pathways associated with the pathogenesis of arthritis. The upregulated genes (n = 1,183) were associated with processes involved in the remodelling of the extracellular matrix and bone mineralization, as well as with the processes of aerobic metabolism. At the histological level, PE attenuated joint inflammatory infiltrate and cartilage erosion. Conclusion. Physical exercise influences parameters intimately linked to inflammatory arthropathies. Research on the effect of PE on the pathogenesis process of arthritis is still necessary for animal and human models. Cite this article:Bone Joint Res. 2020;9(1):36–48


The Bone & Joint Journal
Vol. 104-B, Issue 5 | Pages 604 - 612
1 May 2022
MacDessi SJ Wood JA Diwan A Harris IA

Aims. Intraoperative pressure sensors allow surgeons to quantify soft-tissue balance during total knee arthroplasty (TKA). The aim of this study was to determine whether using sensors to achieve soft-tissue balance was more effective than manual balancing in improving outcomes in TKA. Methods. A multicentre randomized trial compared the outcomes of sensor balancing (SB) with manual balancing (MB) in 250 patients (285 TKAs). The primary outcome measure was the mean difference in the four Knee injury and Osteoarthritis Outcome Score subscales (ΔKOOS. 4. ) in the two groups, comparing the preoperative and two-year scores. Secondary outcomes included intraoperative balance data, additional patient-reported outcome measures (PROMs), and functional measures. Results. There was no significant difference in ΔKOOS. 4. between the two groups at two years (mean difference 0.4 points (95% confidence interval (CI) -4.6 to 5.4); p = 0.869), and multiple regression found that SB was not associated with a significant ΔKOOS. 4. (0.2-point increase (95% CI -5.1 to 4.6); p = 0.924). There were no significant differences between groups in other PROMs. Six-minute walking distance was significantly increased in the SB group (mean difference 29 metres; p = 0.015). Four-times as many TKAs were unbalanced in the MB group (36.8% MB vs 9.4% SB; p < 0.001). Irrespective of group assignment, no differences were found in any PROM when increasing ICPD thresholds defined balance. Conclusion. Despite improved quantitative soft-tissue balance, the use of sensors intraoperatively did not differentially improve the clinical or functional outcomes two years after TKA. These results question whether a more precisely balanced TKA that is guided by sensor data, and often achieved by more balancing interventions, will ultimately have a significant effect on clinical outcomes. Cite this article: Bone Joint J 2022;104-B(5):604–612


Bone & Joint Research
Vol. 10, Issue 2 | Pages 122 - 133
1 Feb 2021
He CP Jiang XC Chen C Zhang HB Cao WD Wu Q Ma C

Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2021;10(2):122–133


Bone & Joint Research
Vol. 5, Issue 12 | Pages 594 - 601
1 Dec 2016
Li JJ Wang BQ Fei Q Yang Y Li D

Objectives. In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis. Methods. We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs. Results. A total of three microarray studies were selected for integrated analysis. In all, 1125 genes were found to be significantly differentially expressed between osteoporosis patients and normal controls, with 373 upregulated and 752 downregulated genes. Positive regulation of the cellular amino metabolic process (gene ontology (GO): 0033240, false discovery rate (FDR) = 1.00E + 00) was significantly enriched under the GO category for biological processes, while for molecular functions, flavin adenine dinucleotide binding (GO: 0050660, FDR = 3.66E-01) and androgen receptor binding (GO: 0050681, FDR = 6.35E-01) were significantly enriched. DEGs were enriched in many osteoporosis-related signalling pathways, including those of mitogen-activated protein kinase (MAPK) and calcium. Protein-protein interaction (PPI) network analysis showed that the significant hub proteins contained ubiquitin specific peptidase 9, X-linked (Degree = 99), ubiquitin specific peptidase 19 (Degree = 57) and ubiquitin conjugating enzyme E2 B (Degree = 57). Conclusion. Analysis of gene function of identified differentially expressed genes may expand our understanding of fundamental mechanisms leading to osteoporosis. Moreover, significantly enriched pathways, such as MAPK and calcium, may involve in osteoporosis through osteoblastic differentiation and bone formation. Cite this article: J. J. Li, B. Q. Wang, Q. Fei, Y. Yang, D. Li. Identification of candidate genes in osteoporosis by integrated microarray analysis. Bone Joint Res 2016;5:594–601. DOI: 10.1302/2046-3758.512.BJR-2016-0073.R1


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 788 - 794
1 Apr 2021
Spierenburg G Lancaster ST van der Heijden L Mastboom MJL Gelderblom H Pratap S van de Sande MAJ Gibbons CLMH

Aims. Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres. Methods. The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019. Results. A total of 84 patients were included. There were 39 men and 45 women with a mean age at primary treatment of 38.3 years (9 to 72). The median follow-up was 46.5 months (interquartile range (IQR) 21.3 to 82.3). Localized-type TGCT (n = 15) predominantly affected forefoot, whereas diffuse-type TGCT (Dt-TGCT) (n = 9) tended to panarticular involvement. TGCT was not included in the radiological differential diagnosis in 20% (n = 15/75). Most patients had open rather than arthroscopic surgery (76 vs 17). The highest recurrence rates were seen with Dt-TGCT (61%; n = 23/38), panarticular involvement (83%; n = 5/8), and after arthroscopy (47%; n = 8/17). Three (4%) fusions were carried out for osteochondral destruction by Dt-TGCT. There were 14 (16%) patients with Dt-TGCT who underwent systemic treatment, mostly in refractory cases (79%; n = 11). TGCT initially decreased or stabilized in 12 patients (86%), but progressed in five (36%) during follow-up; all five underwent subsequent surgery. Side effects were reported in 12 patients (86%). Conclusion. We recommend open surgical excision as the primary treatment for TGCT of the foot and ankle, particularly in patients with Dt-TGCT with extra-articular involvement. Severe osteochondral destruction may justify salvage procedures, although these are not often undertaken. Systemic treatment is indicated for unresectable or refractory cases. However, side effects are commonly experienced, and relapses may occur once treatment has ceased. Cite this article: Bone Joint J 2021;103-B(4):788–794


Bone & Joint Open
Vol. 3, Issue 4 | Pages 291 - 301
4 Apr 2022
Holleyman RJ Lyman S Bankes MJK Board TN Conroy JL McBryde CW Andrade AJ Malviya A Khanduja V

Aims. This study uses prospective registry data to compare early patient outcomes following arthroscopic repair or debridement of the acetabular labrum. Methods. Data on adult patients who underwent arthroscopic labral debridement or repair between 1 January 2012 and 31 July 2019 were extracted from the UK Non-Arthroplasty Hip Registry. Patients who underwent microfracture, osteophyte excision, or a concurrent extra-articular procedure were excluded. The EuroQol five-dimension (EQ-5D) and International Hip Outcome Tool 12 (iHOT-12) questionnaires were collected preoperatively and at six and 12 months post-operatively. Due to concerns over differential questionnaire non-response between the two groups, a combination of random sampling, propensity score matching, and pooled multivariable linear regression models were employed to compare iHOT-12 improvement. Results. A total of 2,025 labral debridements (55%) and 1,659 labral repairs (45%) were identified. Both groups saw significant (p < 0.001) EQ-5D and iHOT-12 gain compared to preoperative scores at 12 months (iHOT-12 improvement: labral repair = +28.7 (95% confidence interval (CI) 26.4 to 30.9), labral debridement = +24.7 (95% CI 22.5 to 27.0)), however there was no significant difference between procedures after multivariable modelling. Overall, 66% of cases achieved the minimum clinically important difference (MCID) and 48% achieved substantial clinical benefit at 12 months. Conclusion. Both labral procedures were successful in significantly improving early functional outcome following hip arthroscopy, regardless of age or sex. Labral repair was associated with superior outcomes in univariable analysis, however there was no significant superiority demonstrated in the multivariable model. Level of evidence: III. Cite this article: Bone Jt Open 2022;3(4):291–301


The Bone & Joint Journal
Vol. 103-B, Issue 6 Supple A | Pages 38 - 44
1 Jun 2021
DeMik DE Carender CN Glass NA Brown TS Callaghan JJ Bedard NA

Aims. The purpose of this study was to assess total knee arthroplasty (TKA) volume and rates of early complications in morbidly obese patients over the last decade, where the introduction of quality models influencing perioperative care pathways occurred. Methods. Patients undergoing TKA between 2011 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program database. Patients were stratified by BMI < 40 kg/m. 2. and ≥ 40 kg/m. 2. and evaluated by the number of cases per year. The 30-day rates of any complication, wound complications, readmissions, and reoperation were assessed. Trends in these endpoints over the study period were compared between groups using odds ratios (ORs) and multivariate analyses. Results. In total, 314,695 patients underwent TKA and 46,362 (15%) had BMI ≥ 40 kg/m. 2. The prevalence of morbid obesity among TKA patients did not change greatly, ranging between 14% and 16%. Reoperation rate decreased from 1.16% to 0.96% (odds ratio (OR) 0.81 (95% confidence interval (CI) 0.66 to 0.99)) for patients with BMI < 40 kg/m. 2. , as did rates of readmission (4.46% to 2.87%; OR 0.61 (0.55 to 0.69)). Patients with BMI ≥ 40 kg/m. 2. also had fewer readmissions over the study period (4.87% to 3.34%; OR 0.64 (0.49 to 0.83)); however, the rate of reoperation did not change (1.37% to 1.41%; OR 0.99 (0.62 to 1.56)). Significant improvements were not observed for infective complications over time for either group; patients with BMI ≥ 40 kg/m. 2. had increased risk of both deep infection and wound complications compared to non-morbidly obese patients. Rate of any complication decreased for all patients. Conclusion. The proportion of TKAs in morbidly obese patients has not significantly changed over the past decade. Although readmission rates improved for all patients, reductions in reoperation in non-morbidly obese patients were not experienced by the morbidly obese, resulting in a widening of the complication gap between these cohorts. Care improvements have not lowered the differential risk of infective complications in the morbidly obese. Cite this article: Bone Joint J 2021;103-B(6 Supple A):38–44


The Bone & Joint Journal
Vol. 99-B, Issue 11 | Pages 1477 - 1481
1 Nov 2017
Hernandez NM Taunton MJ Perry KI Mara KC Hanssen AD Abdel MP

Aims. Patients with flexion instability after total knee arthroplasty (TKA) often present with a recurrent effusion, which may be a haemarthrosis. While the radiographic factors contributing to flexion instability have been elucidated, the clinical diagnosis remains challenging. Our aim, in this study, was to determine the mean white cell count and differential profile in pre-operative aspirations of synovial fluid in a consecutive series of patients undergoing revision TKA for flexion instability. Patients and Methods. Between 2000 and 2010, 60 patients undergoing aseptic revision TKA for flexion instability were identified. The results of the pre-operative aspiration of synovial fluid were available for 53 patients (88%). These patients were 1:2 matched to 106 patients who underwent aseptic TKA for indications other than flexion instability. The mean age of the patients at revision TKA was 65 years (44 to 82) and 55% were women. The mean follow-up was 4.3 years (2 to 10.2). Results. In the flexion instability group, the median total cell count was 312 cells/µL (interquartile range (IQR) 104 to 624), with a mean distribution of 45% macrophages (2% to 90%), 30% lymphocytes (1% to 69%), 18% neutrophils (0% to 80%), 0.5% eosinophils (0% to 6%) and 7% other cells (0% to 42%; mainly synovial cells). There was no significant difference in the median total cell count (p = 0.14) or mean distribution of macrophages (p = 0.42), lymphocytes (p = 0.38), neutrophils (p = 0.19) and eosinophils (p = 0.89) between the flexion instability and control groups. There was a significant difference in the percentage of bloody serosanguineous aspirations which was 58% in the flexion instability group and 18% in the control group (odds ratio = 6.5; p = 0.0001). Conclusions. In the group of patients who underwent revision TKA for flexion instability, most had a mean cell count and differential similar to those who underwent revision for other aseptic indications. However, bloody serosanguineous aspirations were 6.5 times more common in those with flexion instability confirming that many of the recurrent effusions seen in this condition are haemarthroses. Cite this article: Bone Joint J 2017;99-B:1477–81


Bone & Joint Research
Vol. 9, Issue 3 | Pages 130 - 138
1 Mar 2020
Qi X Yu F Wen Y Li P Cheng B Ma M Cheng S Zhang L Liang C Liu L Zhang F

Aims. Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear. Methods. Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools. Results. We detected 33 common genes, eight common gene ontology (GO) terms, and one common pathway for hip OA, such as calcium and integrin-binding protein 1 (CIB1) (PTWAS = 0.025, FCmRNA = -1.575 for skeletal muscle), adrenomedullin (ADM) (PTWAS = 0.022, FCmRNA = -4.644 for blood), Golgi apparatus (PTWAS <0.001, PmRNA = 0.012 for blood), and phosphatidylinositol 3' -kinase-protein kinase B (PI3K-Akt) signalling pathway (PTWAS = 0.033, PmRNA = 0.005 for blood). For knee OA, we detected 24 common genes, eight common GO terms, and two common pathways, such as histocompatibility complex, class II, DR beta 1 (HLA-DRB1) (PTWAS = 0.040, FCmRNA = 4.062 for skeletal muscle), Follistatin-like 1 (FSTL1) (PTWAS = 0.048, FCmRNA = 3.000 for blood), cytoplasm (PTWAS < 0.001, PmRNA = 0.005 for blood), and complement and coagulation cascades (PTWAS = 0.017, PmRNA = 0.001 for skeletal muscle). Conclusion. We identified a group of OA-associated genes and pathways, providing novel clues for understanding the genetic mechanism of OA. Cite this article:Bone Joint Res. 2020;9(3):130–138


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 904 - 911
1 Jul 2020
Sigmund IK Dudareva M Watts D Morgenstern M Athanasou NA McNally MA

Aims. The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition. Methods. A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree. Results. Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 10. 9. /l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases. Conclusion. The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904–911


The Bone & Joint Journal
Vol. 101-B, Issue 7_Supple_C | Pages 17 - 21
1 Jul 2019
Schroer WC LeMarr AR Mills K Childress AL Morton DJ Reedy ME

Aims. To date, no study has demonstrated an improvement in postoperative outcomes following elective joint arthroplasty with a focus on nutritional intervention for patients with preoperative hypoalbuminaemia. In this prospective study, we evaluated differences in the hospital length of stay (LOS), rate of re-admission, and total patient charges for a malnourished patient study population who received a specific nutrition protocol before surgery. Patients and Methods. An analytical report was extracted from the electronic medical record (EMR; Epic, Verona, Wisconsin) of a five-hospital network joint arthroplasty patient data set between 2014 and 2017. A total of 4733 patients underwent joint arthroplasty and had preoperative measurement of albumin levels: 2220 at four hospitals and 2513 at the study hospital. Albumin ≤ 3.4 g/l, designated as malnutrition, was found in 543 patients (11.5%). A nutritional intervention programme focusing on a high-protein, anti-inflammatory diet was initiated in January 2017 at one study hospital. Hospital LOS, re-admission rate, and 90-day charges were compared for differential change between patients in study and control hospitals for all elective hip and knee arthroplasty patients, and for malnourished patients over time as the nutrition intervention was implemented. Results. Malnourished patients with nutritional intervention at the study hospital had shorter hospital LOS beginning in 2017 than malnourished patients at control hospitals during the same period (p = 0.04). Similarly, this cohort had significantly lower primary hospitalization charges, charges associated with hospital re-admissions, and 90-day total charges (p < 0.001). Inclusion of covariant potential confounders (age, anaemia, diabetes, and obesity) did not alter the conclusions of the primary statistical analysis. Conclusion. Joint arthroplasty outcomes were positively affected in study patients with low albumin when a high-protein, anti-inflammatory diet was encouraged. Elective surgery was neither cancelled nor delayed with a malnutrition designation. While the entire network population experienced improved postoperative outcomes, malnourished control patients did not experience this improvement. This study demonstrated that education on malnutrition can benefit patients. Cite this article: Bone Joint J 2019;101-B(7 Supple C):17–21


Bone & Joint Open
Vol. 2, Issue 8 | Pages 569 - 575
1 Aug 2021
Bouguennec N Robinson J Douiri A Graveleau N Colombet PD

Aims. MRI has been suggested as an objective method of assessing anterior crucate ligament (ACL) graft “ligamentization” after reconstruction. It has been proposed that the MRI appearances could be used as an indicator of graft maturity and used as part of a return-to-sport assessment. The aim of this study was to evaluate the correlation between MRI graft signal and postoperative functional scores, anterior knee laxity, and patient age at operation. Methods. A consecutive cohort of 149 patients who had undergone semitendinosus autograft ACL reconstruction, using femoral and tibial adjustable loop fixations, were evaluated retrospectively postoperatively at two years. All underwent MRI analysis of the ACL graft, performed using signal-to-noise quotient (SNQ) and the Howell score. Functional outcome scores (Lysholm, Tegner, International Knee Documentation Committee (IKDC) subjective, and IKDC objective) were obtained and all patients underwent instrumented side-to-side anterior laxity differential laxity testing. Results. Two-year postoperative mean outcome scores were: Tegner 6.5 (2 to 10); Lysholm 89.8 (SD 10.4; 52 to 100); and IKDC subjective 86.8 (SD 11.8; 51 to 100). The objective IKDC score was 86% A (128 patients), 13% B (19 patients), and 1% C (two patients). Mean side-to-side anterior laxity difference (134 N force) was 0.6 mm (SD 1.8; -4.1 to 5.6). Mean graft SNQ was 2.0 (SD 3.5; -14 to 17). Graft Howell scores were I (61%, 91 patients), II (25%, 37 patients), III (13%, 19 patients), and IV (1%, two patients). There was no correlation between either Howell score or SNQ with instrumented anterior or Lysholm, Tegner, and IKDC scores, nor was any correlation found between patient age and ACL graft SNQ or Howell score. Conclusion. The two-year postoperative MRI appearances of four-strand, semitendinosus ACL autografts (as measured by SNQ and Howell score) do not appear to have a relationship with postoperative functional scores, instrumented anterior laxity, or patient age at surgery. Other tools for analysis of graft maturity should be developed. Cite this article: Bone Jt Open 2021;2(8):569–575


Bone & Joint Research
Vol. 7, Issue 11 | Pages 601 - 608
1 Nov 2018
Hsu W Hsu W Hung J Shen W Hsu RW

Objectives. Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. Methods. We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. Results. Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. Conclusion. These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts. Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601–608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2


Bone & Joint Research
Vol. 8, Issue 4 | Pages 179 - 188
1 Apr 2019
Chen M Chang C Yang L Hsieh P Shih H Ueng SWN Chang Y

Objectives. Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. Methods. We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. Results. Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. Conclusion. IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement. Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179–188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1


Bone & Joint Research
Vol. 12, Issue 2 | Pages 91 - 102
1 Feb 2023
Li Z Chen M Wang Z Fan Q Lin Z Tao X Wu J Liu Z Lin R Zhao C

Aims

Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis.

Methods

Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology.


Bone & Joint Research
Vol. 7, Issue 4 | Pages 298 - 307
1 Apr 2018
Zhang X Bu Y Zhu B Zhao Q Lv Z Li B Liu J

Objectives. The aim of this study was to identify key pathological genes in osteoarthritis (OA). Methods. We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the result of bioinformatics analysis. Electronic validation was performed to verify the expression of selected DEGs. The diagnosis value of identified DEGs was accessed by receiver operating characteristic (ROC) analysis. Results. A total of 1085 DEGs were identified. KEGG pathway analysis displayed that Wnt was a significantly enriched signalling pathway. Some hub genes with high interactions such as USP46, CPVL, FKBP5, FOSL2, GADD45B, PTGS1, and ZNF423 were identified in the PPI and TFs network. The results of qRT-PCR showed that GADD45B, ADAMTS1, and TFAM were down-regulated in joint synovial tissues of OA, which was consistent with the bioinformatics analysis. The expression levels of USP46, CPVL, FOSL2, and PTGS1 in electronic validation were compatible with the bio-informatics result. CPVL and TFAM had a potential diagnostic value for OA based on the ROC analysis. Conclusion. The deregulated genes including USP46, CPVL, FKBP5, FOSL2, GADD45B, PTGS1, ZNF423, ADAMTS1, and TFAM might be involved in the pathology of OA. Cite this article: X. Zhang, Y. Bu, B. Zhu, Q. Zhao, Z. Lv, B. Li, J. Liu. Global transcriptome analysis to identify critical genes involved in the pathology of osteoarthritis. Bone Joint Res 2018;7:298–307. DOI: 10.1302/2046-3758.74.BJR-2017-0245.R1


Bone & Joint Research
Vol. 12, Issue 12 | Pages 702 - 711
1 Dec 2023
Xue Y Zhou L Wang J

Aims

Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

Methods

First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers.


Aims

This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously.

Methods

Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes.


Bone & Joint 360
Vol. 12, Issue 5 | Pages 30 - 34
1 Oct 2023

The October 2023 Shoulder & Elbow Roundup360 looks at: Arthroscopic capsular shift surgery in patients with atraumatic shoulder joint instability: a randomized, placebo-controlled trial; Superior capsular reconstruction partially restores native glenohumeral loads in a dynamic model; Gene expression in glenoid articular cartilage varies in acute instability, chronic instability, and osteoarthritis; Intra-articular injection versus interscalene brachial plexus block for acute-phase postoperative pain management after arthroscopic shoulder surgery; Level of pain catastrophizing rehab in subacromial impingement: secondary analyses from a pragmatic randomized controlled trial (the SExSI Trial); Anterosuperior versus deltopectoral approach for primary reverse total shoulder arthroplasty: a study of 3,902 cases from the Dutch National Arthroplasty Registry with a minimum follow-up of five years; Assessment of progression and clinical relevance of stress-shielding around press-fit radial head arthroplasty: a comparative study of two implants; A number of modifiable and non-modifiable factors increase the risk for elbow medial ulnar collateral ligament injury in baseball players: a systematic review.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 372 - 374
8 Jun 2023
Makaram NS Lamb SE Simpson AHRW

Cite this article: Bone Joint Res 2023;12(6):372–374.