Objectives. Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92

Objectives. This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model. Methods. Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR). Results. The OARSI score was significantly lower in mice treated with SRT1720 than in control mice at eight and 12 weeks associated with the decreased size of osteophytes at four and eight weeks. The delayed OA progression in the mice treated with SRT1720 was also associated with increased SIRT1-positive chondrocytes and decreased MMP-13-, ADAMTS-5-, cleaved caspase-3-, PARP p85-, and acetylated NF-κB p65-positive chondrocytes and decreased synovitis at four and eight weeks. SRT1720 treatment partially rescued the decreases in collagen type II alpha 1 (COL2A1) and aggrecan caused by IL-1β, while also reducing the induction of MMP-13 by IL-1β in vitro. Conclusion. The intraperitoneal injection of SRT1720 attenuated experimental OA progression in mice, indicating that SRT1720 could be a new therapeutic approach for OA. Cite this article: K. Nishida, T. Matsushita, K. Takayama, T. Tanaka, N. Miyaji, K. Ibaraki, D. Araki, N. Kanzaki, T. Matsumoto, R. Kuroda. Intraperitoneal injection of the SIRT1 activator SRT1720 attenuates the progression of experimental osteoarthritis in mice. Bone Joint Res 2018;7:252–262. DOI: 10.1302/2046-3758.73.BJR-2017-0227.R1

Aims. The modified Dunn procedure has the potential to restore the anatomy in hips with severe slipped capital femoral epiphyses (SCFE). However, there is a risk of developing avascular necrosis of the femoral head (AVN). In this paper, we report on clinical outcome, radiological outcome, AVN rate and complications, and the cumulative survivorship at long-term follow-up in patients undergoing the modified Dunn procedure for severe SCFE. Patients and Methods. We performed a retrospective analysis involving 46 hips in 46 patients treated with a modified Dunn procedure for severe SCFE (slip angle > 60°) between 1999 and 2016. At nine-year-follow-up, 40 hips were available for clinical and radiological examination. Mean preoperative age was 13 years, and 14 hips (30%) presented with unstable slips. Mean preoperative slip angle was 64°. Kaplan–Meier survivorship was calculated. Results. At the latest follow-up, the mean Merle d’Aubigné and Postel score was 17 points (14 to 18), mean modified Harris Hip Score was 94 points (66 to 100), and mean Hip Disability and Osteoarthritis Outcome Score was 91 points (67 to 100). Postoperative slip angle was 7° (1° to 16°). One hip (2%) had progression of osteoarthritis (OA). Two hips (5%) developed AVN of the femoral head and required further surgery. Three other hips (7%) underwent implant revision due to screw breakage or change of wires. Cumulative survivorship was 86% at ten-year follow-up. Conclusion. The modified Dunn procedure for severe SCFE resulted in a low rate of AVN, low risk of progression to OA, and high functional scores at long-term follow-up. The slip deformities were mainly corrected but secondary impingement deformities can develop in some hips and may require further surgical treatment. Cite this article: Bone Joint J 2019;101-B:403–414

Objectives. Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes in vitro. Methods. Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed. Results. Using LA or GC, especially triamcinolone acetonide, a dilution of 1:100 resulted in only a moderate reduction of viability, while a dilution of 1:10 showed significantly fewer cell counts. TA and CA reduced viability significantly at a dilution of 1:2. Higher dilutions did not affect viability. Notably, HA showed no effects of cytotoxicity in all drug dilutions. Conclusion. The toxicity of common intra-articular injectable drugs, assessed by cell viability, is mainly dependent on the dilution of the drug being tested. LA are particularly toxic, whereas HA did not affect cell viability. Cite this article: P. Busse, C. Vater, M. Stiehler, J. Nowotny, P. Kasten, H. Bretschneider, S. B. Goodman, M. Gelinsky, S. Zwingenberger. Cytotoxicity of drugs injected into joints in orthopaedics. Bone Joint Res 2019;8:41–48. DOI: 10.1302/2046-3758.82.BJR-2018-0099.R1

Aims. Tibiotalocalcaneal (TTC) fusion is used to treat a variety of conditions affecting the ankle and subtalar joint, including osteoarthritis (OA), Charcot arthropathy, avascular necrosis (AVN) of the talus, failed total ankle arthroplasty, and severe deformity. The prevalence of postoperative complications remains high due to the complexity of hindfoot disease seen in these patients. The aim of this study was to analyze the relationship between preoperative conditions and postoperative complications in order to predict the outcome following primary TTC fusion. Methods. We retrospectively reviewed the medical records of 101 patients who underwent TTC fusion at the same institution between 2011 and 2019. Risk ratios (RRs) associated with age, sex, diabetes, cardiovascular disease, smoking, preoperative ankle deformity, and the use of bone graft during surgery were related to the postoperative complications. We determined from these data which pre- and perioperative factors significantly affected the outcome. Results. Out of the 101 patients included in the study, 29 (28.7%) had nonunion, five (4.9%) required below-knee amputation (BKA), 40 (39.6%) returned to the operating theatre, 16 (15.8%) had hardware failure, and 22 (21.8%) had a postoperative infection. Patients with a preoperative diagnosis of Charcot arthropathy and non-traumatic OA had significantly higher nonunion rates of 44.4% (12 patients) and 39.1% (18 patients) (p = 0.016) and infection rates of 29.6% (eight patients) and 37% (17 patients) compared to patients with traumatic arthritis, respectively (p = 0.002). There was a significantly increased rate of nonunion in diabetic patients (RR 2.22; p = 0.010). Patients with chronic kidney disease were 2.37-times more likely to have a nonunion (p = 0.006). Patients aged over 60 years had more than a three-fold increase in the rate of postoperative infection (RR 3.60; p = 0.006). The use of bone graft appeared to be significantly protective against postoperative infection (p = 0.019). Conclusion. We were able to confirm, in the largest series of TTC ankle fusions currently in the literature, that there remains a high rate of complications following this procedure. We found that patients with a Charcot or non-traumatic arthropathy had an increased risk of nonunion and postoperative infection compared to individuals with traumatic arthritis. Those with diabetes, chronic kidney disease, or aged over 60 years had an increased risk of nonunion. These findings help to confirm those of previous studies. Additionally, our study adds to the literature by showing that autologous bone graft may help in decreasing infection rates. These data can be useful to surgeons and patients when considering, discussing and planning TTC fusion. It helps surgeons further understand which patients are at a higher risk for postoperative complications when undergoing TTC fusion. Cite this article: Bone Joint J. 2020;102-B(3):345–351

Objectives. Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats. Methods. Rat OA was induced by performing meniscectomy surgery while cartilage samples were collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were determined by using enzyme-linked immunosorbent assay, while other proteins were assessed by using Western blot. Results. In the time course of the study, nitric oxide was increased seven and 14 days after OA induction. Pro-inflammatory cytokines including tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were decreased. L-NG-Nitroarginine methyl ester (L-NAME, a non-specific nitric oxide synthase inhibitor) significantly decreased cartilage nitric oxide and blocked immune suppression. Further, L-NAME decreased Matrix metalloproteinase (MMPs) and increased tissue inhibitor of metalloproteinase (TIMP) expression in meniscectomised rats. Conclusion. Nitric oxide-dependent innate immune suppression protects cartilage from damage in the early stages of OA initiation in rats. Cite this article: C-C. Hsu, C-L. Lin, I-M. Jou, P-H. Wang, J-S. Lee. The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in ca rtilage da mage. Bone Joint Res 2017;6:253–258. DOI: 10.1302/2046-3758.64.BJJ-2016-0161.R1

Aims. Custom flange acetabular components (CFACs) are a patient-specific option for addressing large acetabular defects at revision total hip arthroplasty (THA), but patient and implant characteristics that affect survivorship remain unknown. This study aimed to identify patient and design factors related to survivorship. Patients and Methods. A retrospective review of 91 patients who underwent revision THA using 96 CFACs was undertaken, comparing features between radiologically failed and successful cases. Patient characteristics (demographic, clinical, and radiological) and implant features (design characteristics and intraoperative features) were collected. There were 74 women and 22 men; their mean age was 62 years (31 to 85). The mean follow-up was 24.9 months (. sd. 27.6; 0 to 116). Two sets of statistical analyses were performed: 1) univariate analyses (Pearson’s chi-squared and independent-samples Student’s t-tests) for each feature; and 2) bivariable logistic regressions using features identified from a random forest analysis. Results. Radiological failure and revision rates were 23% and 12.5%, respectively. Revisions were undertaken at a mean of 25.1 months (. sd. 26.4) postoperatively. Patients with radiological failure were younger at the time of the initial procedure, were less likely to have a diagnosis of primary osteoarthritis (OA), were more likely to have had ischial screws in previous surgery, had fewer ischial screw holes in their CFAC design, and had more proximal ischial fixation. Random forest analysis identified the age of the patient and the number of locking and non-locking screws used for inclusion in subsequent bivariable logistic regression, but only age (odds ratio 0.93 per year) was found to be significant. Conclusion. We identified both patient and design features predictive of CFAC survivorship. We found a higher rate of failure in younger patients, those whose primary diagnosis was not OA, and those with more proximal ischial fixation or fewer ischial fixation options. Cite this article: Bone Joint J 2019;101-B(6 Supple B):68–76

Aims. This study of patients with osteoarthritis (OA) of the hip aimed to: 1) characterize the contribution of the hip, spinopelvic complex, and lumbar spine when moving from the standing to the sitting position; 2) assess whether abnormal spinopelvic mobility is associated with worse symptoms; and 3) identify whether spinopelvic mobility can be predicted from static anatomical radiological parameters. Patients and Methods. A total of 122 patients with end-stage OA of the hip awaiting total hip arthroplasty (THA) were prospectively studied. Patient-reported outcome measures (PROMs; Oxford Hip Score, Oswestry Disability Index, and Veterans RAND 12-Item Health Survey Score) and clinical data were collected. Sagittal spinopelvic mobility was calculated as the change from the standing to sitting position using the lumbar lordosis angle (LL), sacral slope (SS), pelvic tilt (PT), pelvic-femoral angle (PFA), and acetabular anteinclination (AI) from lateral radiographs. The interaction of the different parameters was assessed. PROMs were compared between patients with normal spinopelvic mobility (10° ≤ ∆PT ≤ 30°) or abnormal spinopelvic mobility (stiff: ∆PT < ± 10°; hypermobile: ∆PT > ± 30°). Multiple regression and receiver operating characteristic (ROC) curve analyses were used to test for possible predictors of spinopelvic mobility. Results. Standing to sitting, the hip flexed by a mean of 57° (. sd. 17°), the pelvis tilted backwards by a mean of 20° (. sd. 12°), and the lumbar spine flexed by a mean of 20° (. sd. 14°); strong correlations were detected. There was no difference in PROMs between patients in the different spinopelvic mobility groups. Maximum hip flexion, standing PT, and standing AI were independent predictors of spinopelvic mobility (R. 2. = 0.42). The combined thresholds for standing was PT ≥ 13° and hip flexion ≥ 88° in the clinical examination, and had 90% sensitivity and 63% specificity of predicting spinopelvic stiffness, while SS ≥ 42° had 84% sensitivity and 67% specificity of predicting spinopelvic hypermobility. Conclusion. The hip, on average, accounts for three-quarters of the standing-to-sitting movement, but there is great variation. Abnormal spinopelvic mobility cannot be screened with PROMs. However, clinical and standing radiological features can predict spinopelvic mobility with good enough accuracy, allowing them to be used as reliable screening tools. Cite this article: Bone Joint J 2019;101-B:902–909

Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions. Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589

Objectives. Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA. Methods. Patients with OA at the base of the thumb, or the hip, underwent preoperative MRI to assess BMLs, and tetracycline labelling to determine bone turnover. Three groups were compared: trapezium bones removed by trapeziectomy from patients with thumb base OA (n = 20); femoral heads with (n = 24); and those without (n = 9) BMLs obtained from patients with hip OA who underwent total hip arthroplasty. Results. All trapezium bones demonstrated MRI-defined BMLs. Compared with femoral heads without BMLs, the trapezia demonstrated significantly higher bone turnover (mean . sd. 0.2 (0.1) versus 0.01 (0.01) µm. 3. /µm. 2. /day), mineralizing surface (18.5% (13.1) versus 1.4% (1.3)) and vascularity (5.2% (1.1) versus 1.2% (0.6)). Femoral heads with BMLs exhibited higher bone turnover (0.3 (0.2) versus 0.2 (0.1) µm. 3. /µm. 2. /day), a higher mineralization rate (26.6% (10.6) versus 18.6% (11.9)) and greater trabecular thickness (301.3 µm (108) versus 163.6 µm (24.8)) than the trapezia. Conclusion. Bone turnover and angiogenesis were enhanced in BMLs of both the thumb base and hip OA, of which the latter exhibited the highest bone turnover. Thus, the increase in bone turnover in weight-bearing joints like the hip may be more pronounced than less mechanically loaded osteoarthritic joints demonstrating BMLs. The histological changes observed may explain the water signal from BMLs on MRI. Cite this article: M. Shabestari, N. J. Kise, M. A. Landin, S. Sesseng, J. C. Hellund, J. E. Reseland, E. F. Eriksen, I. K. Haugen. Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb. Bone Joint Res 2018;7:406–413. DOI: 10.1302/2046-3758.76.BJR-2017-0083.R3

Aims. To report mid- to long-term results of Oxford mobile bearing domed lateral unicompartmental knee arthroplasty (UKA), and determine the effect of potential contraindications on outcome. Methods. A total of 325 consecutive domed lateral UKAs undertaken for the recommended indications were included, and their functional and survival outcomes were assessed. The effects of age, weight, activity, and the presence of full-thickness erosions of cartilage in the patellofemoral joint on outcome were evaluated. Results. Median follow-up was seven years (3 to 14), and mean age at surgery was 65 years (39 to 90). Median Oxford Knee Score (OKS) was 43 (interquartile range (IQR) 37 to 47), with 260 (80%) achieving a good or excellent score (OKS > 34). Revisions occurred in 34 (10%); 14 (4%) were for dislocation, of which 12 had no recurrence following insertion of a new bearing, and 12 (4%) were revised for medial osteoarthritis (OA). Ten-year survival was 85% (95% confidence interval (CI) 79 to 90, at risk 72). Age, weight, activity, and patellofemoral erosions did not have a significant effect on the clinical outcome or survival. Conclusion. Domed lateral UKA provides a good alternative to total knee arthroplasty (TKA) in the management of lateral compartment OA. Although dislocation is relatively easy to treat successfully, the dislocation rate of 4% is high. It is recommended that the stability of the bearing is assessed intraoperatively. If the bearing can easily be displaced, the fixed rather than the mobile bearing version of the Oxford lateral tibial component should be inserted instead. Younger age, heavier weight, high activity, and patellofemoral erosions did not detrimentally affect outcome, so should not be considered contraindications. Cite this article: Bone Joint J 2020;102-B(8):1033–1040

Aims. Total hip arthroplasty (THA) is gaining popularity as a treatment for displaced femoral neck fractures (FNFs), especially in physiologically younger patients. While THA for osteoarthritis (OA) has demonstrated low complication rates and increased quality of life, results of THA for acute FNF are not as clear. Currently, a THA performed for FNF is included in an institutional arthroplasty bundle without adequate risk adjustment, potentially placing centres participating in fracture care at financial disadvantage. The purpose of this study is to report on perioperative complication rates after THA for FNF compared with elective THA performed for OA of the hip. Patients and Methods. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database between 2008 and 2016 was queried. Patients were identified using the THA Current Procedural Terminology (CPT) code and divided into groups by diagnosis: OA in one and FNF in another. Univariate statistics were performed. Continuous variables were compared between groups using Student’s t-test, and the chi-squared test was used to compare categorical variables. Multivariate and propensity-matched logistic regression analyses were performed to control for risk factors of interest. Results. Analyses included 139 635 patients undergoing THA. OA was the indication in 135 013 cases and FNF in 4622 cases. After propensity matching, mortality within 30 days (1.8% vs 0.3%; p < 0.001) and major morbidity (24.2% vs 19%; p < 0.001) were significantly higher among FNF patients. Re-operation (3.7% vs 2.7%; p = 0.014) and re-admission (7.3% vs 5.5%; p = 0.002) were significantly higher among FNF patients. Hip fracture patients had significantly longer operative time and length of stay (LOS), and were significantly less likely to be discharged to their home. Multivariate analyses gave similar results. Conclusion. This large database study showed a higher risk of postoperative complications including mortality, major morbidity, re-operation, re-admission, prolonged operative time, increased LOS, and decreased likelihood of discharge home in patients undergoing THA for FNF compared with OA. While THA is a good option for FNF patients, there are increased costs and financial risks to centres with a joint arthroplasty bundle programme participating in fracture care. Cite this article: Bone Joint J 2019;101-B(6 Supple B):84–90

Aims. It has been hypothesized that a unicompartmental knee arthroplasty (UKA) is more likely to be revised than a total knee arthroplasty (TKA) because conversion surgery to a primary TKA is a less complicated procedure. The purpose of this study was to determine if there is a lower threshold for revising a UKA compared with TKA based on Oxford Knee Scores (OKSs) and range of movement (ROM) at the time of revision. Methods. We retrospectively reviewed 619 aseptic revision cases performed between December 1998 and October 2018. This included 138 UKAs that underwent conversion to TKA and 481 initial TKA revisions. Age, body mass index (BMI), time in situ, OKS, and ROM were available for all patients. Results. There were no differences between the two groups based on demographics or time to revision. The top reasons for aseptic TKA revision were loosening in 212 (44%), instability in 88 (18%), and wear in 69 (14%). UKA revision diagnoses were primarily for loosening in 50 (36%), progression of osteoarthritis (OA) in 50 (36%), and wear in 17 (12%). Out of a maximum 48 points, the mean OKS of the UKAs before revision was 23 (SD 9.3), which was significantly higher than the TKAs at 19.2 (SD 9.8; p < 0.001). UKA patients scored statistically better on nine of the 12 individual OKS questions. The UKA cases also had a larger pre-revision mean ROM (114°, SD 14.3°) than TKAs (98°, SD 25°) ; p < 0.001). Conclusion. At revision, the mean UKA OKSs and ROM were significantly better than those of TKA cases. This study suggests that at our institution there is a difference in preoperative OKS between UKA and TKA at the time of revision, demonstrating a revision bias. Cite this article: Bone Joint J 2020;102-B(6 Supple A):91–95

Objectives. This study aimed to explore the role of miR-320a in the pathogenesis of osteoarthritis (OA). Methods. Human cartilage cells (C28/I2) were transfected with miR-320a or antisense oligonucleotides (ASO)-miR-320a, and treated with IL-1β. Subsequently the expression of collagen type II alpha 1 (Col2α1) and aggrecan (ACAN), and the concentrations of sulfated glycosaminoglycans (sGAG) and matrix metallopeptidase 13 (MMP-13), were assessed. Luciferase reporter assay, qRT-PCR, and Western blot were performed to explore whether pre-B-cell leukemia Homeobox 3 (PBX3) was a target of miR-320a. Furthermore, cells were co-transfected with miR-320a and PBX3 expressing vector, or cells were transfected with miR-320a and treated with a nuclear factor kappa B (NF-κB) antagonist MG132. The changes in Col2α1 and ACAN expression, and in sGAG and MMP-13 concentrations, were measured again. Statistical comparisons were made between two groups by using the two-tailed paired t-test. Results. Expression of miR-320a was elevated in OA cartilage tissues and chondrocytes, and in IL-1β-stimulated C28/I2 cells (p < 0.05 or p < 0.01). MiR-320a overexpression enhanced IL-1β-induced down-regulation of Col2α1 and ACAN and sGAG, and increased the IL-1β-induced overexpression of MMP-13 (p < 0.01). PBX3 was a direct target of miR-320a. PBX3 and MG132 co-transfection attenuated the effects of miR-320a on the expression of Col2α1, ACAN, sGAG and MMP-13(p < 0.01). Conclusion. Overexpression of miR-320a might enhance IL-1β-induced cartilage degradation factors. These effects might be via targeting PBX3 and regulating NF-κB. Cite this article: Y. Jin, X. Chen, Z. Y. Gao, K. Liu, Y. Hou, J. Zheng. The role of miR-320a and IL-1β in human chondrocyte degradation. Bone Joint Res 2017;6:–203. DOI: 10.1302/2046-3758.64.BJR-2016-0224.R1

Aim. Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods. Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results. We identified 1265 differentially methylated genes, of which 145 are associated with significant changes in gene expression, such as DLX5, NCOR2 and AXIN2 (all p-values of both DNA methylation and mRNA expression < 0.05). Pathway enrichment analysis identified 26 OA-associated pathways, such as mitogen-activated protein kinase (MAPK) signalling pathway (p = 6.25 × 10-4), phosphatidylinositol (PI) signalling system (p = 4.38 × 10-3), hypoxia-inducible factor 1 (HIF-1) signalling pathway (p = 8.63 × 10-3 pantothenate and coenzyme A (CoA) biosynthesis (p = 0.017), ErbB signalling pathway (p = 0.024), inositol phosphate (IP) metabolism (p = 0.025), and calcium signalling pathway (p = 0.032). Conclusion. We identified a group of genes and biological pathwayswhich were significantly different in both DNA methylation and mRNA expression profiles between patients with OA and controls. These results may provide new clues for clarifying the mechanisms involved in the development of OA. Cite this article: A. He, Y. Ning, Y. Wen, Y. Cai, K. Xu, Y. Cai, J. Han, L. Liu, Y. Du, X. Liang, P. Li, Q. Fan, J. Hao, X. Wang, X. Guo, T. Ma, F. Zhang. Use of integrative epigenetic and mRNA expression analyses to identify significantly changed genes and functional pathways in osteoarthritic cartilage. Bone Joint Res 2018;7:343–350. DOI: 10.1302/2046-3758.75.BJR-2017-0284.R1

Aims. Recently, there has been considerable interest in quantifying the associations between bony abnormalities around and in the hip joint and osteoarthritis (OA). Our aim was to investigate the relationships between acetabular undercoverage, acetabular overcoverage, and femoroacetabular impingement (FAI) with OA of the hip, which currently remain controversial. . Materials and Methods. A total of 545 cadaveric skeletons (1090 hips) from the Hamann-Todd osteological collection were obtained. Femoral head volume (FHV), acetabular volume (AV), the FHV/AV ratio, acetabular version, alpha angle and anterior femoral neck offset (AFNO) were measured. A validated grading system was used to quantify OA of the hip as minimal, moderate, or severe. Multiple linear and multinomial logistic regression were used to determine the factors that correlated independently with the FHV, AV, and the FHV/AV ratio. . Results. Female cadavers had smaller FHVs (standardised beta -0.382, p < 0.001), and AVs (standardised beta -0.351, p < 0.001), compared with male patients, although the FHV/AV ratio was unchanged. Every 1° increase in alpha angle increased the probability of having moderate OA of the hip compared with minimal OA by 7.1%. Every 1 mm decrease in AFNO increased the probability of having severe or moderate OA of the hip, compared with minimal OA, by 11% and 9%, respectively. The relative risk ratios of having severe OA of the hip compared with minimal OA were 7.2 and 3.3 times greater for acetabular undercoverage and overcoverage, respectively, relative to normal acetabular cover. . Conclusion . Acetabular undercoverage and overcoverage were independent predictors of increased OA of the hip. The alpha angle and AFNO had modest effects, supporting the hypothesis that bony abnormalities both in acetabular dysplasia and FAI are associated with severe OA. Cite this article: Bone Joint J 2017;99-B:432–9

We studied whether the presence of lateral osteophytes on plain radiographs was a predictor for the quality of cartilage in the lateral compartment of patients with varus osteoarthritic of the knee (Kellgren and Lawrence grade 2 to 3). The baseline MRIs of 344 patients from the Osteoarthritis Initiative (OAI) who had varus osteoarthritis (OA) of the knee on hip-knee-ankle radiographs were reviewed. Patients were categorised using the Osteoarthritis Research Society International (OARSI) osteophyte grading system into 174 patients with grade 0 (no osteophytes), 128 grade 1 (mild osteophytes), 28 grade 2 (moderate osteophytes) and 14 grade 3 (severe osteophytes) in the lateral compartment (tibia). All patients had Kellgren and Lawrence grade 2 or 3 arthritis of the medial compartment. The thickness and volume of the lateral cartilage and the percentage of full-thickness cartilage defects in the lateral compartment was analysed. There was no difference in the cartilage thickness or cartilage volume between knees with osteophyte grades 0 to 3. The percentage of full-thickness cartilage defects on the tibial side increased from < 2% for grade 0 and 1 to 10% for grade 3. The lateral compartment cartilage volume and thickness is not influenced by the presence of lateral compartment osteophytes in patients with varus OA of the knee. Large lateral compartment osteophytes (grade 3) increase the likelihood of full-thickness cartilage defects in the lateral compartment. Cite this article: Bone Joint J 2015;97-B:1634–9

There have been several studies examining the association between the morphological characteristics seen in acetabular dysplasia and the incidence of the osteoarthritis (OA). However, most studies focus mainly on acetabular morphological analysis, and few studies have scrutinised the effect of femoral morphology. In this study we enrolled 36 patients with bilateral acetabular dysplasia and early or mid-stage OA in one hip and no OA in the contralateral hip. CT scans were performed from the iliac crest to 2 cm inferior to the tibial tuberosity, and the morphological characteristics of both acetabulum and femur were studied. . In addition, 200 hips in 100 healthy volunteer Chinese adults formed a control group. The results showed that the dysplastic group with OA had a significantly larger femoral neck anteversion and a significantly shorter abductor lever arm than both the dysplastic group without OA and the controls. Femoral neck anteversion had a significant negative correlation with the length of the abductor lever arm and we conclude that it may contribute to the development of OA in dysplastic hips. Cite this article: Bone Joint J 2014; 96-B:1586–93

Treatment for osteoarthritis (OA) has traditionally focused on joint replacement for end-stage disease. An increasing number of surgical and pharmaceutical strategies for disease prevention have now been proposed. However, these require the ability to identify OA at a stage when it is potentially reversible, and detect small changes in cartilage structure and function to enable treatment efficacy to be evaluated within an acceptable timeframe. This has not been possible using conventional imaging techniques but recent advances in musculoskeletal imaging have been significant. In this review we discuss the role of different imaging modalities in the diagnosis of the earliest changes of OA. The increasing number of MRI sequences that are able to non-invasively detect biochemical changes in cartilage that precede structural damage may offer a great advance in the diagnosis and treatment of this debilitating condition. Cite this article: Bone Joint J 2013;95-B:738–46

The purpose of this study was to evaluate the effect of various non-operative modalities of treatment (transcutaneous electrical nerve stimulation (TENS); neuromuscular electrical stimulation (NMES); insoles and bracing) on the pain of osteoarthritis (OA) of the knee. . We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify the therapeutic options which are commonly adopted for the management of osteoarthritis (OA) of the knee. The outcome measurement tools used in the different studies were the visual analogue scale and The Western Ontario and McMaster Universities Arthritis Index pain index: all pain scores were converted to a 100-point scale. . A total of 30 studies met our inclusion criteria: 13 on insoles, seven on TENS, six on NMES, and four on bracing. The standardised mean difference (SMD) in pain after treatment with TENS was 1.796, which represented a significant reduction in pain. The significant overall effect estimate for NMES on pain was similar to that of TENS, with a SMD of 1.924. The overall effect estimate of insoles on pain was a SMD of 0.992. The overall effect of bracing showed a significant reduction in pain of 1.34. . Overall, all four non-operative modalities of treatment were found to have a significant effect on the reduction of pain in OA of the knee. . This study shows that non-operative physical modalities of treatment are of benefit when treating OA of the knee. However, much of the literature reviewed evaluates studies with follow-up of less than six months: future work should aim to evaluate patients with longer follow-up. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):89–94