Aims. The aetiologies of common degenerative spine, hip, and knee pathologies are still not completely understood. Mechanical theories have suggested that those diseases are related to sagittal pelvic morphology and spinopelvic-femoral dynamics. The link between the most widely used parameter for sagittal pelvic morphology, pelvic incidence (PI), and the onset of degenerative lumbar, hip, and knee pathologies has not been studied in a large-scale setting. Methods. A total of 421 patients from the Cohort Hip and Cohort Knee (CHECK) database, a population-based observational cohort, with hip and knee complaints < 6 months, aged between 45 and 65 years old, and with lateral lumbar, hip, and knee radiographs available, were included. Sagittal spinopelvic parameters and pathologies (spondylolisthesis and degenerative disc disease (DDD)) were measured at eight-year follow-up and characteristics of hip and knee osteoarthritis (OA) at baseline and eight-year follow-up. Epidemiology of the degenerative disorders and clinical outcome scores (hip and knee pain and Western Ontario and McMaster Universities Osteoarthritis Index) were compared between low PI (< 50°), normal PI (50° to 60°), and high PI (> 60°) using generalized estimating equations. Results. Demographic details were not different between the different PI groups. L4 to L5 and L5 to S1 spondylolisthesis were more frequently present in subjects with high PI compared to low PI (L4 to L5, OR 3.717; p = 0.024 vs L5 to S1 OR 7.751; p = 0.001). L5 to S1 DDD occurred more in patients with low PI compared to high PI (OR 1.889; p = 0.010), whereas there were no differences in L4 to L5 DDD among individuals with a different PI. The incidence of hip OA was higher in participants with low PI compared to normal (OR 1.262; p = 0.414) or high PI (OR 1.337; p = 0.274), but not statistically different. The incidence of knee OA was higher in individuals with a high PI compared to low PI (OR 1.620; p = 0.034). Conclusion. High PI is a risk factor for development of spondylolisthesis and knee OA. Low pelvic incidence is related to DDD, and may be linked to OA of the hip. Level of Evidence: 1b. Cite this article: Bone Joint J 2020;102-B(9):1261–1267

Objectives. The aim of this study was to provide a comprehensive understanding of alterations in messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in cartilage affected by osteoarthritis (OA). Methods. The expression profiles of mRNAs, lncRNAs, and circRNAs in OA cartilage were assessed using whole-transcriptome sequencing. Bioinformatics analyses included prediction and reannotation of novel lncRNAs and circRNAs, their classification, and their placement into subgroups. Gene ontology and pathway analysis were performed to identify differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs). We focused on the overlap of DEGs and targets of DELs previously identified in seven high-throughput studies. The top ten DELs were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in articular chondrocytes, both in vitro and in vivo. Results. In total, 739 mRNAs, 1152 lncRNAs, and 42 circRNAs were found to be differentially expressed in OA cartilage tissue. Among these, we identified 18 overlapping DEGs and targets of DELs, and the top ten DELs were screened by expression profile analysis as candidate OA-related genes. WISP2, ATF3, and CHI3L1 were significantly increased in both normal versus OA tissues and normal versus interleukin (IL)-1β-induced OA-like cell models, while ADAM12, PRELP, and ASPN were shown to be significantly decreased. Among the identified DELs, we observed higher expression of ENST00000453554 and MSTRG.99593.3, and lower expression of MSTRG.44186.2 and NONHSAT186094.1 in normal versus OA cells and tissues. Conclusion. This study revealed expression patterns of coding and noncoding RNAs in OA cartilage, which added sets of genes and noncoding RNAs to the list of candidate diagnostic biomarkers and therapeutic agents for OA patients. Cite this article: H. Li, H. H. Yang, Z. G. Sun, H. B. Tang, J. K. Min. Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients. Bone Joint Res 2019;8:290–303. DOI: 10.1302/2046-3758.87.BJR-2018-0297.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

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

Aims. There is little information about how to manage patients with a recurvatum deformity of the distal tibia and osteoarthritis (OA) of the ankle. The aim of this study was to evaluate the functional and radiological outcome of addressing this deformity using a flexion osteotomy and to assess the progression of OA after this procedure. Patients and Methods. A total of 39 patients (12 women, 27 men; mean age 47 years (28 to 72)) with a distal tibial recurvatum deformity were treated with a flexion osteotomy, between 2010 and 2015. Nine patients (23%) subsequently required conversion to either a total ankle arthroplasty (seven) or an arthrodesis (two) after a mean of 21 months (9 to 36). A total of 30 patients (77%), with a mean follow-up of 30 months (24 to 76), remained for further evaluation. Functional outcome, sagittal ankle joint OA using a modified Kellgren and Lawrence Score, tibial lateral surface (TLS) angle, and talar offset ratio (TOR) were evaluated on pre- and postoperative weight-bearing radiographs. Results. Postoperatively, the mean score for pain, using a visual analogue scale, decreased significantly from 4.3 to 2.5 points and the mean American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score improved significantly from 59 to 75 points (both p < 0.001). The mean TLS angle increased significantly by 6.6°; the mean TOR decreased significantly by 0.24 (p < 0.001). Radiological evaluation showed an improvement or no progression of sagittal ankle joint OA in 32 ankles (82%), while seven ankles (18%) showed further progression. Conclusion. A flexion osteotomy effectively improved the congruency of the ankle joint. In 30 patients (77%), the joint could be saved, whereas in nine patients (23%), the treatment delayed a joint-sacrificing procedure. Cite this article: Bone Joint J 2019;101-B:682–690

Aims. This study investigates the effects of intra-articular injection of adipose-derived mesenchymal stem cells (AdMSCs) and platelet-rich plasma (PRP) on lameness, pain, and quality of life in osteoarthritic canine patients. Methods. With informed owner consent, adipose tissue collected from adult dogs diagnosed with degenerative joint disease was enzymatically digested and cultured to passage 1. A small portion of cells (n = 4) surplus to clinical need were characterized using flow cytometry and tri-lineage differentiation. The impact and degree of osteoarthritis (OA) was assessed using the Liverpool Osteoarthritis in Dogs (LOAD) score, Modified Canine Osteoarthritis Staging Tool (mCOAST), kinetic gait analysis, and diagnostic imaging. Overall, 28 joints (25 dogs) were injected with autologous AdMSCs and PRP. The patients were followed up at two, four, eight, 12, and 24 weeks. Data were analyzed using two related-samples Wilcoxon signed-rank or Mann-Whitney U tests with statistical significance set at p < 0.05. Results. AdMSCs demonstrated stem cell-like characteristics. LOAD scores were significantly lower at week 4 compared with preinjection (p = 0.021). The mCOAST improved significantly after three months (p = 0.001) and six months (p = 0.001). Asymmmetry indices decreased from four weeks post-injection and remained significantly lower at six months (p = 0.025). Conclusion. These improvements in quality of life, reduction in pain on examination, and improved symmetry in dogs injected with AdMSCs and PRP support the effectiveness of this combined treatment for symptom modification in canine OA for six months. Cite this article: Bone Joint Res 2021;10(10):650–658

Aims. Spinopelvic mobility plays an important role in functional acetabular component position following total hip arthroplasty (THA). The primary aim of this study was to determine if spinopelvic hypermobility persists or resolves following THA. Our second aim was to identify patient demographic or radiological factors associated with hypermobility and resolution of hypermobility after THA. Methods. This study investigated patients with preoperative posterior hypermobility, defined as a change in sacral slope (SS) from standing to sitting (ΔSS. stand-sit. ) ≥ 30°. Radiological spinopelvic parameters, including SS, pelvic incidence (PI), lumbar lordosis (LL), PI-LL mismatch, anterior pelvic plane tilt (APPt), and spinopelvic tilt (SPT), were measured on preoperative imaging, and at six weeks and a minimum of one year postoperatively. The severity of bilateral hip osteoarthritis (OA) was graded using Kellgren-Lawrence criteria. Results. A total of 136 patients were identified as having preoperative spinopelvic hypermobility. At one year after THA, 95% (129/136) of patients were no longer categorized as hypermobile on standing and sitting radiographs (ΔSS. stand-sit. < 30°). Mean ΔSS. stand-sit. decreased from 36.4° (SD 5.1°) at baseline to 21.4° (SD 6.6°) at one year (p < 0.001). Mean SS. seated. increased from baseline (11.4° (SD 8.8°)) to one year after THA by 11.5° (SD 7.4°) (p < 0.001), which correlates to an 8.5° (SD 5.5°) mean decrease in seated functional cup anteversion. Contralateral hip OA was the only radiological predictor of hypermobility persisting at one year after surgery. The overall reoperation rate was 1.5%. Conclusion. Spinopelvic hypermobility was found to resolve in the majority (95%) of patients one year after THA. The increase in SS. seated. was clinically significant, suggesting that current target recommendations for the hypermobile patient (decreased anteversion and inclination) should be revisited. Cite this article: Bone Joint J 2021;103-B(12):1766–1773

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. The use and variety of stemless humeral components in anatomical total shoulder arthroplasty (TSA) have proliferated since their advent in 2004. Early outcomes are reassuring but independent mid-term results are scarce. This independent study reports a consecutive series of 143 Eclipse stemless shoulder prostheses with a minimum five-year (5 to 10) follow-up. Methods. Outcomes of 143 procedures undertaken for all indications in 131 patients were reviewed, with subset analysis of those for osteoarthritis (OA) (n = 99). The primary outcome was the Oxford Shoulder Score (OSS) at a minimum of five years. Secondary outcomes were ranges of motion and radiological analysis of humeral radiolucency, rotator cuff failure, and glenoid loosening. Results. Mean OSS at mean follow-up of 6.67 years (5.0 to 10.74) was 40.12 (9 to 48), with no statistically significant difference between those implanted for a non-OA indication and those for OA (p = 0.056) or time-dependent deterioration between two years and five years (p = 0.206). Ranges of motion significantly improved compared with preoperative findings and were maintained between two and five years with a mean external rotation of 38° (SD 18.1, 0 to 100) and forward elevation of 152° (SD 29.9, 90 to 180). Of those components with radiographs suitable for analysis (n = 83), 23 (28%) were found to have a least one humeral radiolucent line, which were predominantly incomplete, less than 2 mm, and in a single anatomical zone. No humeral components were loose. A radiolucent line was present around 22 (15%) of glenoid components, and 15 (10%) of components had failed. Rotator cuff failure was found in 21 (15%) components. The mean time to either glenoid or rotator cuff failure was greater than three years following implantation. Survivorship was 96.4% (95% CI 91.6 to 98.5, number at risk 128) at five years, and 94.3% (95% CI 88.2 to 97.3, number at risk 76) at seven years, both of which compare favourably with best results taken from available registries. Conclusion. Functional and radiological outcomes of the Eclipse stemless TSA are excellent, with no loose humeral components at minimum five-year follow-up. The presence of radiolucent lines is of interest and requires long-term observation but does not impact on the clinical results. Of the eight revisions required, this was predominantly for glenoid and rotator cuff failure. Cite this article: Bone Joint J 2022;104-B(1):83–90

Aims. Patients may present with concurrent symptomatic osteoarthritis (OA) of the hip and degenerative disorders of the lumbar spine, with surgical treatment being indicated for both. Whether arthroplasty of the hip or spinal surgery should be performed first remains uncertain. Materials and Methods. Clinical scenarios were devised for a survey asking the preferred order of surgery and the rationale for this decision for five fictional patients with both OA of the hip and degenerative lumbar disorders. These were symptomatic OA of the hip and: 1) lumbar spinal stenosis with neurological claudication; 2) lumbar degenerative spondylolisthesis with leg pain; 3) lumbar disc herniation with leg weakness; 4) lumbar scoliosis with back pain; and 5) thoracolumbar disc herniation with myelopathy. This survey was sent to 110 members of The Hip Society and 101 members of the Scoliosis Research Society. The choices of the surgeons were compared among scenarios and between surgical specialties using the chi-squared test. The free-text comments were analyzed using text-mining. Results. Responses were received from 51 hip surgeons (46%) and 37 spine surgeons (37%). The percentages of hip surgeons recommending ‘hip first’ differed significantly among scenarios: 59% for scenario 1; 73% for scenario 2; 47% for scenario 3; 47% for scenario 4; and 10% for scenario 5 (p < 0.001). The percentages of spine surgeons recommending ‘hip first’ were 49% for scenario 1; 70% for scenario 2; 19% for scenario 3; 78% for scenario 4; and 0% for scenario 5. There were significant differences between the groups for scenarios 3 (more hip surgeons recommended ‘hip first’; p = 0.012) and 4 (more hip surgeons recommended ‘spine first’; p = 0.006). Conclusion. In patients with coexistent OA of the hip and degenerative disorders of the spine, the question of ‘hip or spinal surgery first’ elicits relatively consistent answers in some clinical scenarios, but remains controversial in others, even for experienced surgeons. The nature of neurological symptoms can influence surgeons’ decision-making. Cite this article: Bone Joint J 2019;101-B(6 Supple B):37–44

Aims. The aim of this study was to record the incidence of post-traumatic osteoarthritis (OA), the need for total hip arthroplasty (THA), and patient-reported outcome measures (PROMS) after surgery for a fracture of the acetabulum, in our centre. Patients and Methods. All patients who underwent surgery for an acetabular fracture between 2004 and 2014 were included. Patients completed the 36-Item Short Form Health Survey (SF-36) and the modified Harris Hip Score (mHHS) questionnaires. A retrospective chart and radiographic review was performed on all patients. CT scans were used to assess the classification of the fracture and the quality of reduction. Results. A total of 220 patients were included, of which 55 (25%) developed post-traumatic OA and 33 (15%) underwent THA. A total of 164 patients completed both questionnaires. At a mean follow-up of six years (2 to 10), the mean SF-36 score for patients with a preserved hip joint was higher on role limitations due to physical health problems than for those with OA or those who underwent THA. In the dimension of bodily pain, patients with OA had a significantly better score than those who underwent THA. Patients with a preserved hip joint had a significantly better score on the function scale of the mHHS and a better total score than those with OA or who underwent THA. Conclusion. Of the patients who were treated surgically for an acetabular fracture (with a mean follow-up of six years), 15% underwent THA at a mean of 2.75 years postoperatively. Patients with a THA had a worse functional outcome than those who retain their native hip joint. We recommend using PROMS and CT scans when reviewing these patients. Cite this article: Bone Joint J 2018;100-B:640–5

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

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

Objectives. The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. Methods. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. Results. A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. Conclusion. Mechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation. Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1

Aims. The aim of this study was to analyze the results of two radiocapitellar prostheses in a large case series followed prospectively, with medium-term follow-up. Patients and Methods. A total of 31 patients with a mean age of 54 years (27 to 73) were analyzed; nine had primary osteoarthritis (OA) and 17 had post-traumatic OA, three had capitellar osteonecrosis, and two had a fracture. Overall, 17 Lateral Resurfacing Elbow (LRE) and 14 Uni-Elbow Radio-Capitellum Implant (UNI-E) arthroplasties were performed. Pre- and postoperative assessment involved the Mayo Elbow Performance Score (MEPS), the Quick Disabilities of the Arm, Shoulder and Hand (Q-DASH) score, and the modified American Shoulder Elbow Surgeons (m-ASES) score. Results. The mean follow-up was 6.8 years (3.8 to 11.5). The mean MEPS, m-ASES, and Q-DASH scores improved significantly by 50 (p < 0.001), 55 (p < 0.001), and 54 points (p < 0.001), respectively, with no differences being detected between the implants. Preoperative pronation and supination were worse in patients in whom the UNI-E was used. Two patients with the UNI-E implant had asymptomatic evidence of gross loosening. Conclusion. Radiocapitellar arthroplasty yielded a significant improvement in elbow function at a mean follow-up of 6.8 years, with a high implant survival rate when the LRE was used in patients with primary or post-traumatic OA, without radial head deformity, and when the UNI-E was used in patients in whom radial head excision was indicated. Cite this article: Bone Joint J 2019;101-B:1362–1369

Objectives. Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results. Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion. Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218–224. DOI: 10.1302/2046-3758.56.BJR-2015-0001

Aims. The aims of this study were to investigate the ability to kneel after total knee arthroplasty (TKA) without patellar resurfacing, and its effect on patient-reported outcome measures (PROMs). Secondary aims included identifying which kneeling positions were most important to patients, and the influence of radiological parameters on the ability to kneel before and after TKA. Methods. This prospective longitudinal study involved 209 patients who underwent single radius cruciate-retaining TKA without patellar resurfacing. Preoperative EuroQol five-dimension questionnaire (EQ-5D), Oxford Knee Score (OKS), and the ability to achieve four kneeling positions were assessed including a single leg kneel, a double leg kneel, a high-flexion kneel, and a praying position. The severity of radiological osteoarthritis (OA) was graded and the pattern of OA was recorded intraoperatively. The flexion of the femoral component, posterior condylar offset, and anterior femoral offset were measured radiologically. At two to four years postoperatively, 151 patients with a mean age of 70.0 years (SD 9.44) were included. Their mean BMI was 30.4 kg/m. 2. (SD 5.36) and 60 were male (40%). They completed EQ-5D, OKS, and Kujala scores, assessments of the ability to kneel, and a visual analogue scale for anterior knee pain and satisfaction. Results. The ability to kneel in the four positions improved in between 29 (19%) and 53 patients (35%) after TKA, but declined in between 35 (23%) and 46 patients (30%). Single-leg kneeling was most important to patients. After TKA, 62 patients (41%) were unable to achieve a single-leg kneel, 76 (50%) were unable to achieve a double-leg kneel, 102 (68%) were unable to achieve a high-flexion kneel and 61 (40%) were unable to achieve a praying position. Posterolateral cartilage loss significantly affected preoperative deep flexion kneeling (p = 0.019). A postoperative inability to kneel was significantly associated with worse OKS, Kujala scores, and satisfaction (p < 0.05). Multivariable regression analysis identified significant independent associations with the ability to kneel after TKA (p < 0.05): better preoperative EQ-5D and flexion of the femoral component for single-leg kneeling; the ability to achieve it preoperatively and flexion of the femoral component for double-leg kneeling; male sex for high-flexion kneeling; and the ability to achieve it preoperatively, anterior femoral offset, and patellar cartilage loss for the praying position. Conclusion. The ability to kneel was important to patients and significantly influenced knee-specific PROMs, but was poorly restored by TKA with equal chances of improvement or decline. Cite this article: Bone Joint J 2021;103-B(9):1514–1525

Aims. The patient-acceptable symptom state (PASS) is a level of wellbeing, which is measured by the patient. The aim of this study was to determine if the proportion of patients who achieved an acceptable level of function (PASS) after medial unicompartmental knee arthroplasty (UKA) was different based on the status of the anterior cruciate ligament (ACL) at the time of surgery. Methods. A total of 114 patients who underwent UKA for isolated medial osteoarthritis (OA) of the knee were included in the study. Their mean age was 65 years (SD 10). No patient underwent a bilateral procedure. Those who had undergone ACL reconstruction during the previous five years were excluded. The Knee injury Osteoarthritis Outcome Score Activities of Daily Living (KOOS ADL) function score was used as the primary outcome measure with a PASS of 87.5, as described for total knee arthroplasty (TKA). Patients completed all other KOOS subscales, Lysholm score, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Veterans Rand 12-item health survey score. Failure was defined as conversion to TKA. Results. Survivorship at ten years was 97% in both the ACL-deficient and ACL-intact groups. The mean survival was 16.1 years (95% confidence interval (CI) 15.3 to 16.8) for the ACL-deficient group and 15.6 years (95% CI 14.8 to 16.361) for the ACL-intact group (p = 0.878). At a mean of nine years (SD 3.5) in the ACL-deficient group, 32 patients (87%) reached the PASS for the KOOS ADL. In the ACL-intact group, at a mean of 8.6 years (SD 3) follow-up, 63 patients (85%) reached PASS for the KOOS ADL. There was no significant difference in the percentage of patients who reached PASS for all KOOS subscales and Lysholm between the two groups. Conclusion. PASS was achieved in 85% of all UKAs for KOOS ADL, similar to reports for TKA. Fixed-bearing, medial, non-robotically-assisted UKA resulted in 97% survival at ten years in both the ACL-deficient and ACL-intact groups. There was no significant difference in all outcomes between the two groups. Understanding PASS will allow better communication between surgeons and patients to improve the surgical management of patients with single compartment OA of the knee. This study provides mid- to long-term data supporting the use of PASS to document outcomes following UKA. PASS was met in more than 85% of patients with no differences between ACL-deficient and ACL-intact knees at a mean follow-up of nine years. Cite this article: Bone Joint J 2021;103-B(8):1367–1372

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

Aims. Many patients undergoing total knee arthroplasty (TKA) have severe osteoarthritis (OA) in both knees and may consider either simultaneous or staged bilateral TKA. The implications of simultaneous versus staged bilateral TKA for return to work are not well understood. We hypothesized that employed patients who underwent simultaneous bilateral TKA would have significantly fewer days missed from work compared with the sum of days missed from each operation for patients who underwent staged bilateral TKA. Methods. The prospective arthroplasty registry at the Hospital for Special Surgery was used. Baseline characteristics and patient-reported outcome scores were evaluated. We used a linear regression model, adjusting for potential confounding variables including age, sex, preoperative BMI, and type of work (sedentary, moderate, high activity, or strenuous), to analyze time lost from work after simultaneous compared with staged bilateral TKA. Results. We identified 152 employed patients who had undergone simultaneous bilateral TKA and 61 who had undergone staged bilateral TKA, and had completed the registry’s return to work questionnaire. The simultaneous group missed a mean of 46.2 days (SD 29.1) compared with the staged group who missed a mean total of 68.0 days of work (SD 46.1) when combining both operations. This difference was statistically significant (p < 0.001). In multivariate mixed regression analysis adjusted for age, sex, BMI, American Society of Anesthesiologists status, and type of work, the simultaneous group missed a mean of 16.9 (SD 5.7) fewer days of work compared with the staged group (95% confidence interval 5.8 to 28.1; p = 0.003). Conclusion. Employed patients undergoing simultaneous bilateral TKA missed a mean of 17 fewer days of work as a result of their surgical treatment and rehabilitation compared with those undergoing staged bilateral TKA. This information may be useful to surgeons counselling employed patients with bilateral OA of the knee who are considering surgical treatment. Cite this article: Bone Joint J 2021;103-B(6 Supple A):108–112