Aims. To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics. Methods. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSW. L. ) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%. Results. The mean age was 80.6 years (SD 8.3), with 84 females and 79 males. The mean JSW. L. was 5.6 mm (SD 1.4), and was not significantly related to age, sex, or intraoperative findings. Those with BMI > 40 kg/m. 2. had a smaller JSW. L. than those with a ‘normal’ BMI (p = 0.039). The incidence of severe and moderate lateral OA were both 4.9%. Overall, 2/142 (1.4%) of those with nil/mild lateral OA, 1/8 (13%) with moderate, and 2/8 (25%) with severe subsequently had a revision. Those with severe (mean OKS 35.6 (SD 9.3)) and moderate OA (mean OKS 35.8 (SD 10.5)) tended to have worse outcome scores than those with nil/mild (mean OKS 39.5 (SD 9.2)) but the difference was only significant for OKS-Function (p = 0.044). Conclusion. This study showed that the rate of having severe or moderate radiological lateral OA at 15 years after medial UKA was low (both 4.9%). Although patients with severe or moderate lateral OA had a lower OKS than those with nil/mild OA, their mean scores (OKS 36) would be classified as good. Cite this article: Bone Jt Open 2023;4(3):210–218

Aims. Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. Methods. After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. Results. In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. Conclusion. Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA. Cite this article: Bone Joint Res 2023;12(2):121–132

Aims. Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear. Methods. Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis. Results. Abnormal adipogenesis, characterized by increased expression of CCAAT/enhancer-binding protein α (CEBPα), fatty acid binding protein 4 (FABP4), Perilipin1, Adiponectin (AdipoQ), and peroxisome proliferator-activated receptor γ (PPARγ), was enhanced in the degenerative cartilage of TMJ OA in UAC mice, accompanied by decreased expression of GDF11. After FFSS stimulation, there were fat droplets in the cytoplasm of cultured cells with increased expression of PPARγ, CEBPα, FABP4, Perilipin1, and AdipoQ and decreased expression of GDF11. Exogenous GDF11 inhibited increased lipid droplets and expression of AdipoQ, CEBPα, and FABP4 induced by FFSS stimulation. GDF11 did not affect the change in PPARγ expression under FFSS, but promoted its post-translational modification by small ubiquitin-related modifier (SUMOylation). Local injection of GDF11 alleviated TMJ OA-related cartilage degeneration and abnormal adipogenesis in UAC mice. Conclusion. Abnormal adipogenesis of chondrocytes and decreased GDF11 expression were observed in degenerative cartilage of TMJ OA. GDF11 supplementation effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration. GDF11 may inhibit the abnormal adipogenesis of chondrocytes by affecting the SUMOylation of PPARγ. Cite this article: Bone Joint Res 2022;11(7):453–464

Aims. The aim of this study was to determine whether there is a correlation between the grade of humeral osteoarthritis (OA) and the severity of glenoid morphology according to Walch. We hypothesized that there would be a correlation. Methods. Overal, 143 shoulders in 135 patients (73 females, 62 males) undergoing shoulder arthroplasty surgery for primary glenohumeral OA were included consecutively. Mean age was 69.3 years (47 to 85). Humeral head (HH), osteophyte length (OL), and morphology (transverse decentering of the apex, transverse, or coronal asphericity) on radiographs were correlated to the glenoid morphology according to Walch (A1, A2, B1, B2, B3), glenoid retroversion, and humeral subluxation on CT images. Results. Increased humeral OL correlated with a higher grade of glenoid morphology (A1-A2-B1-B2-B3) according to Walch (r = 0.672; p < 0.0001). It also correlated with glenoid retroversion (r = 0.707; p < 0.0001), and posterior humeral subluxation (r = 0.452; p < 0.0001). A higher humeral OL (odds ratio (OR) 1.17; 95% confidence interval (CI) 1.03 to 1.32; p = 0.013), posterior humeral subluxation (OR 1.11; 95% CI 1.01 to 1.22; p = 0.031), and glenoid retroversion (OR 1.48; 95% CI 1.30 to 1.68; p < 0.001) were independent factors for a higher glenoid morphology. More specifically, a humeral OL of ≥ 13 mm was indicative of eccentric glenoid types B2 and B3 (OR 14.20; 95% CI 5.96 to 33.85). Presence of an aspherical HH in the coronal plane was suggestive of glenoid types B2 and B3 (OR 3.34; 95% CI 1.67 to 6.68). Conclusion. The criteria of humeral OL and HH morphology are associated with increasing glenoid retroversion, posterior humeral subluxation, and eccentric glenoid wear. Therefore, humeral radiological parameters might hint at the morphology on the glenoid side. Cite this article: Bone Jt Open 2022;3(6):463–469

Aims. The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Methods. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results. A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion. This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371

Aims. The aim of this study was to report the pooled prevalence of post-traumatic osteoarthritis (PTOA) and examine whether the risk of developing PTOA after anterior cruciate ligament (ACL) injury has decreased in recent decades. Methods. The PubMed and Web of Science databases were searched from 1 January 1980 to 11 May 2022. Patient series, observational studies, and clinical trials having reported the prevalence of radiologically confirmed PTOA after ACL injury, with at least a ten-year follow-up, were included. All studies were analyzed simultaneously, and separate analyses of the operative and nonoperative knees were performed. The prevalence of PTOA was calculated separately for each study, and pooled prevalence was reported with 95% confidence intervals (CIs) using either a fixed or random effects model. To examine the effect of the year of injury on the prevalence, a logit transformed meta-regression analysis was used with a maximum-likelihood estimator. Results from meta-regression analyses were reported with the unstandardized coefficient (β). Results. The pooled prevalence of PTOA was 37.9% (95% CI 32.1 to 44) for operatively treated ACL injuries with a median follow-up of 14.6 years (interquartile range (IQR) 10.6 to 16.7). For nonoperatively treated ACL injuries, the prevalence was 40.5% (95% CI 28.9 to 53.3), with a median of follow-up of 15 years (IQR 11.7 to 20.0). The association between the year of operation and the prevalence of PTOA was weak and imprecise and not related to the choice of treatment (operative β -0.038 (95% CI -0.076 to 0.000) and nonoperative β -0.011 (95% CI -0.101 to 0.079)). Conclusion. The initial injury, irrespective of management, has, by the balance of probability, resulted in PTOA within 20 years. In addition, the prevalence of PTOA has only slightly decreased during past decades. Therefore, further research is warranted to develop strategies to prevent the development of PTOA after ACL injuries. Cite this article: Bone Joint J 2023;105-B(11):1140–1148

Aims. This study aimed to investigate the incidence of ≥ 5 mm asymmetry in lower and whole leg lengths (LLs) in patients with unilateral osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH-OA) and primary hip osteoarthritis (PHOA), and the relationship between lower and whole LL asymmetries and femoral length asymmetry. Methods. In total, 116 patients who underwent unilateral total hip arthroplasty were included in this study. Of these, 93 had DDH-OA and 23 had PHOA. Patients with DDH-OA were categorized into three groups: Crowe grade I, II/III, and IV. Anatomical femoral length, femoral length greater trochanter (GT), femoral length lesser trochanter (LT), tibial length, foot height, lower LL, and whole LL were evaluated using preoperative CT data of the whole leg in the supine position. Asymmetry was evaluated in the Crowe I, II/III, IV, and PHOA groups. Results. The incidences of whole and lower LL asymmetries were 40%, 62.5%, 66.7%, and 26.1%, and 21.7%, 20.8%, 55.6%, and 8.7% in the Crowe I, II/III, and IV, and PHOA groups, respectively. The incidence of tibial length asymmetry was significantly higher in the Crowe IV group (44.4%) than that in the PHOA group (4.4%). In all, 50% of patients with DDH-OA with femoral length GT and LT asymmetries had lower LL asymmetry, and 75% had whole LL asymmetry. The incidences of lower and whole LL asymmetries were 20% and 42.9%, respectively, even in the absence of femoral length GT and LT asymmetries. Conclusion. Overall, 43% of patients with unilateral DDH-OA without femoral length asymmetry had whole LL asymmetry of ≥ 5 mm. Thus, both the femur length and whole LL should be measured to accurately assess LL discrepancy in patients with unilateral DDH-OA. Cite this article: Bone Jt Open 2024;5(2):79–86

Aims. This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA). Methods. Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model. Results. We discovered for the first time that MCL was substantially enriched in the synovial fluid of OA patients and promoted the release of inflammatory cytokines from FLSs through MCL phagocytosis. Through LC‒MS, ANT3 was identified and determined to be significantly upregulated in MCL and OA-FLSs, corresponding to impaired mitochondrial function and cell viability in OA-FLSs. Mitochondrial homeostasis was restored by ANT3 suppression, thereby alleviating synovial inflammation. Furthermore, elevated ANT3 levels inhibited ERK phosphorylation. Specifically, silencing ANT3 prevented inhibition of ERK phosphorylation and significantly reduced the elevation of reactive oxygen species (ROS) and JC1 membrane potential in MCL-induced synovial inflammation. Conclusion. This study revealed the important roles of MCL and ANT3 in FLS mitochondria. Silencing ANT3 rescued ERK phosphorylation, thereby restoring mitochondrial homeostasis in FLSs and alleviating synovitis and OA development, offering a potential target for treating synovitis and preventing early-stage OA. Cite this article: Bone Joint Res 2023;12(4):274–284

Aims. The objective of this study was to present the outcomes of rotational acetabular osteotomy (RAO) over a 30-year period for osteoarthritis (OA) secondary to dysplasia of the hip in pre- or early-stage OA. Methods. Between September 1987 and December 1994, we provided treatment to 47 patients (55 hips) with RAO for the management of pre- or early-stage OA due to developmental hip dysplasia. Of those, eight patients (11 hips) with pre-OA (follow-up rate 79%) and 27 patients (32 hips) with early-stage OA (follow-up rate 78%), totalling 35 patients (43 hips) (follow-up rate 78%), were available at a minimum of 28 years after surgery. Results. In the pre-OA group, the mean Merle d'Aubigné score improved significantly from 14.5 points (SD 0.7) preoperatively to 17.4 points at final follow-up (SD 1.2; p = 0.004) and in the early-stage group, the mean score did not improve significantly from 14.0 (SD 0.3) to 14.6 (SD 2.4; p = 0.280). Radiologically, the centre-edge angle, acetabular roof angle, and head lateralization index were significantly improved postoperatively in both groups. Radiological progression of OA was observed in two patients (two hips) in the pre-OA group and 17 patients (18 hips) in the early-stage group. Kaplan-Meier survival analysis, with radiological progression of OA as the primary outcome, projected a 30-year survival rate of 81.8% (95% confidence interval (CI) 0.59 to 1.00) for the pre-OA group and 42.2% (95% CI 0.244 to 0.600) for the early-stage group. In all cases, the overall survival rate stood at 51.5% (95% CI 0.365 to 0.674) over a 30-year period, and when the endpoint was conversion to total hip arthroplasty, the survival rate was 74.0% (95% CI 0.608 to 0.873). Conclusion. For younger patients with pre-OA, joint preservation of over 30 years can be expected after RAO. Cite this article: Bone Joint J 2024;106-B(5 Supple B):25–31

Aims. Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2. -/-. ) display accelerated bone growth. Methods. We examined vulnerability of Socs2. -/-. mice to OA following surgical induction of disease (destabilization of the medial meniscus (DMM)), and with ageing, by histology and micro-CT. Results. We observed a significant increase in mean number (wild-type (WT) DMM: 532 (SD 56); WT sham: 495 (SD 45); knockout (KO) DMM: 169 (SD 49); KO sham: 187 (SD 56); p < 0.001) and density (WT DMM: 2.2 (SD 0.9); WT sham: 1.2 (SD 0.5); KO DMM: 13.0 (SD 0.5); KO sham: 14.4 (SD 0.7)) of growth plate bridges in Socs2. -/-. in comparison with WT. Histological examination of WT and Socs2. -/-. knees revealed articular cartilage damage with DMM in comparison to sham. Articular cartilage lesion severity scores (mean and maximum) were similar in WT and Socs2. -/-. mice with either DMM, or with ageing. Micro-CT analysis revealed significant decreases in SCB thickness, epiphyseal trabecular number, and thickness in the medial compartment of Socs2. -/-. , in comparison with WT (p < 0.001). DMM had no effect on the SCB thickness in comparison with sham in either genotype. Conclusion. Together, these data suggest that enhanced GH signalling through SOCS2 deletion accelerates growth plate fusion, however this has no effect on OA vulnerability in this model. Cite this article: Bone Joint Res 2022;11(3):162–170

Aims. In recent years, the use of a collared cementless femoral prosthesis has risen in popularity. The design intention of collared components is to transfer some load to the resected femoral calcar and prevent implant subsidence within the cancellous bone of the metaphysis. Conversely, the load transfer for a cemented femoral prosthesis depends on the cement-component and cement-bone interface interaction. The aim of our study was to compare the three most commonly used collared cementless components and the three most commonly used tapered polished cemented components in patients aged ≥ 75 years who have undergone a primary total hip arthroplasty (THA) for osteoarthritis (OA). Methods. Data from the Australian Orthopaedic Association National Joint Replacement Registry from 1 September 1999 to 31 December 2022 were analyzed. Collared cementless femoral components and cemented components were identified, and the three most commonly used components in each group were analyzed. We identified a total of 11,278 collared cementless components and 47,835 cemented components. Hazard ratios (HRs) from Cox proportional hazards models, adjusting for age and sex, were obtained to compare the revision rates between the groups. Results. From six months postoperatively onwards, patients aged ≥ 75 years undergoing primary THA with primary diagnosis of OA have a lower risk of all-cause revision with collared cementless components than with a polished tapered cemented component (HR 0.78 (95% confidence interval 0.64 to 0.96); p = 0.018). There is no difference in revision rate prior to six months. Conclusion. Patients aged ≥ 75 years with a primary diagnosis of OA have a significantly lower rate of revision with the most common collared cementless femoral component, compared with the most common polished tapered cemented components from six months postoperatively onwards. The lower revision rate is largely due to a reduction in revisions for fracture and infection. Cite this article: Bone Joint J 2024;106-B(3 Supple A):121–129

Aims. Deciphering the genetic relationships between major depressive disorder (MDD) and osteoarthritis (OA) may facilitate an understanding of their biological mechanisms, as well as inform more effective treatment regimens. We aim to investigate the mechanisms underlying relationships between MDD and OA in the context of common genetic variations. Methods. Linkage disequilibrium score regression was used to test the genetic correlation between MDD and OA. Polygenic analysis was performed to estimate shared genetic variations between the two diseases. Two-sample bidirectional Mendelian randomization analysis was used to investigate causal relationships between MDD and OA. Genomic loci shared between MDD and OA were identified using cross-trait meta-analysis. Fine-mapping of transcriptome-wide associations was used to prioritize putatively causal genes for the two diseases. Results. MDD has a significant genetic correlation with OA (r. g. = 0.29) and the two diseases share a considerable proportion of causal variants. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on OA (b. xy. = 0.24) and genetic liability to OA conferred a causal effect on MDD (b. xy. = 0.20). Cross-trait meta-analyses identified 29 shared genomic loci between MDD and OA. Together with fine-mapping of transcriptome-wide association signals, our results suggest that Estrogen Receptor 1 (ESR1), SRY-Box Transcription Factor 5 (SOX5), and Glutathione Peroxidase 1 (GPX1) may have therapeutic implications for both MDD and OA. Conclusion. The study reveals substantial shared genetic liability between MDD and OA, which may confer risk for one another. Our findings provide a novel insight into phenotypic relationships between MDD and OA. Cite this article: Bone Joint Res 2022;11(1):12–22

Aims. This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. Methods. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed. Results. A total of 88 DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were significantly enriched in leucocyte migration and interleukin (IL)-17 signalling pathways. Disease ontology (DO) indicated that DEGs were mostly enriched in rheumatoid arthritis. Six hub genes including FosB proto-oncogene, AP-1 transcription factor subunit (FOSB); C-X-C motif chemokine ligand 2 (CXCL2); CXCL8; IL-6; Jun proto-oncogene, AP-1 transcription factor subunit (JUN); and Activating transcription factor 3 (ATF3) were identified and verified by GEO datasets. ATF3 (area under the curve = 0.975) turned out to be a potential biomarker for the diagnosis of early OA. Several infiltrating immune cells varied significantly between early-stage OA and end-stage OA, such as resting NK cells (p = 0.016), resting dendritic cells (p = 0.043), and plasma cells (p = 0.043). Additionally, ATF3 was significantly correlated with resting NK cells (p = 0.034), resting dendritic cells (p = 0.026), and regulatory T cells (Tregs, p = 0.018). Conclusion. ATF3 may be a potential diagnostic marker for early diagnosis and treatment of OA, and immune cell infiltration provides new perspectives for understanding the mechanism during OA progression. Cite this article: Bone Joint Res 2022;11(9):679–689

Aims. Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA. Methods. Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro. Results. IL-38 was highly expressed in lentivirus vector-mediated OA mice. Meanwhile, injection of exogenous IL-38 to OA mice alleviated the cartilage damage, and reduced the levels of proinflammatory factors and chondrocyte apoptosis. TP53 was responsible for lncRNA H19-mediated upregulation of IL-38. Furthermore, it was found that the anti-inflammatory effects of IL-38 were achieved by its binding with the IL-36 receptor (IL-36R). Overexpression of H19 reduced the expression of inflammatory factors and chondrocyte apoptosis, which was abrogated by knockdown of IL-38 or TP53. Conclusion. Collectively, our findings evidenced that upregulation of lncRNA H19 attenuates inflammation and ameliorates cartilage damage and chondrocyte apoptosis in OA by upregulating TP53, IL-38, and by activating IL-36R. Cite this article: Bone Joint Res 2022;11(8):594–607

Aims. The aim of this study was to determine whether total hip arthroplasty (THA) for chronic hip pain due to unilateral primary osteoarthritis (OA) has a beneficial effect on cognitive performance. Methods. A prospective cohort study was conducted with 101 patients with end-stage hip OA scheduled for THA (mean age 67.4 years (SD 9.5), 51.5% female (n = 52)). Patients were assessed at baseline as well as after three and months. Primary outcome was cognitive performance measured by d2 Test of Attention at six months, Trail Making Test (TMT), FAS-test, Rivermead Behavioural Memory Test (RBMT; story recall subtest), and Rey-Osterrieth Complex Figure Test (ROCF). The improvement of cognitive performance was analyzed using repeated measures analysis of variance. Results. At six months, there was significant improvement in attention, working speed and concentration (d2-test; p < 0.001), visual construction and visual memory (ROCF; p < 0.001), semantic memory (FAS-test; p = 0.009), verbal episodic memory (RBMT; immediate recall p = 0.023, delayed recall p = 0.026), as well as pain (p < 0.001) with small to large effect sizes. Attention, concentration, and visual as well as verbal episodic memory improved significantly with medium effect sizes over η. 2. partial. = 0.06. In these cognitive domains the within-group difference exceeded the minimum clinically important difference. Conclusion. THA is associated with clinically relevant postoperative improvement in the cognitive functions of attention, concentration, and memory. These data support the concept of a broad interaction of arthroplasty with central nervous system function. Cite this article: Bone Joint J 2022;104-B(3):331–340

Aims. The aim of this study was to determine the clinical outcomes and factors contributing to failure of transposition osteotomy of the acetabulum (TOA), a type of spherical periacetabular osteotomy, for advanced osteoarthritis secondary to hip dysplasia. Methods. We reviewed patients with Tönnis grade 2 osteoarthritis secondary to hip dysplasia who underwent TOA between November 1998 and December 2019. Patient demographic details, osteotomy-related complications, and the modified Harris Hip Score (mHHS) were obtained via medical notes review. Radiological indicators of hip dysplasia were assessed using preoperative and postoperative radiographs. The cumulative probability of TOA failure (progression to Tönnis grade 3 or conversion to total hip arthroplasty) was estimated using the Kaplan-Meier product-limited method. A multivariate Cox proportional hazards model was used to identify predictors of failure. Results. This study included 127 patients (137 hips). Median follow-up period was ten years (IQR 6 to 15). The median mHHS improved from 59 (IQR 52 to 70) preoperatively to 90 (IQR 73 to 96) at the latest follow-up (p < 0.001). The survival rate was 90% (95% CI 82 to 95) at ten years, decreasing to 21% (95% CI 7 to 48) at 20 years. Fair joint congruity on preoperative hip abduction radiographs and a decreased postoperative anterior wall index (AWI) were identified as independent risk factors for failure. The survival rate for the 42 hips with good preoperative joint congruity and a postoperative AWI ≥ 0.30 was 100% at ten years, and remained at 83% (95% CI 38 to 98) at 20 years. Conclusion. Although the overall clinical outcomes of TOA in patients with advanced osteoarthritis are suboptimal, favourable results can be achieved in selected cases with good preoperative joint congruity and adequate postoperative anterior acetabular coverage. Cite this article: Bone Joint J 2024;106-B(8):783–791

Aims. Tert-butylhydroquinone (tBHQ) has been identified as an inhibitor of oxidative stress-induced injury and apoptosis in human neural stem cells. However, the role of tBHQ in osteoarthritis (OA) is unclear. This study was carried out to investigate the role of tBHQ in OA. Methods. OA animal model was induced by destabilization of the medial meniscus (DMM). Different concentrations of tBHQ (25 and 50 mg/kg) were intraperitoneally injected in ten-week-old female mice. Chondrocytes were isolated from articular cartilage of mice and treated with 5 ng/ml lipopolysaccharide (LPS) or 10 ng/ml interleukin 1 beta (IL-1β) for 24 hours, and then treated with different concentrations of tBHQ (10, 20, and 40 μM) for 12 hours. The expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured. The expression levels of interleukin 6 (IL-6), IL-1β, and tumour necrosis factor alpha (TNF-α) leptin in plasma were measured using enzyme-linked immunoabsorbent assay (ELISA) kits. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway proteins, and macrophage repolarization-related markers, were detected by western blot. Results. Tert-butylhydroquinone significantly attenuated cartilage destruction in DMM-induced mice in vivo. It demonstrated clear evidence of inhibiting IL-1β-induced chondrocyte apoptosis, inflammation, and differentiation defect in vitro. Meanwhile, tBHQ inhibited LPS-induced activation of NF-κB and MAPK signalling pathways, and also inhibited LPS-induced reactive oxygen species production and macrophages repolarization in vitro. Conclusion. Taken together, tBHQ might be a potential therapeutic strategy for protecting against OA development. Cite this article: Bone Joint Res 2021;10(11):704–713

Aims. Both anatomical and reverse total shoulder arthroplasty (aTSA and rTSA) provide functional improvements. A reported benefit of aTSA is better range of motion (ROM). However, it is not clear which procedure provides better outcomes in patients with limited foward elevation (FE). The aim of this study was to compare the outcome of aTSA and rTSA in patients with glenohumeral osteoarthritis (OA), an intact rotator cuff, and limited FE. Methods. This was a retrospective review of a single institution’s prospectively collected shoulder arthroplasty database for TSAs undertaken between 2007 and 2020. A total of 344 aTSAs and 163 rTSAs, which were performed in patients with OA and an intact rotator cuff with a minimum follow-up of two years, were included. Using the definition of preoperative stiffness as passive FE ≤ 105°, three cohorts were matched 1:1 by age, sex, and follow-up: stiff aTSAs (85) to non-stiff aTSAs (85); stiff rTSAs (74) to non-stiff rTSAs (74); and stiff rTSAs (64) to stiff aTSAs (64). We the compared ROMs, outcome scores, and complication and revision rates. Results. Compared with non-stiff aTSAs, stiff aTSAs had poorer passive FE and active external rotation (ER), whereas there were no significant postoperative differences between stiff rTSAs and non-stiff rTSAs. There were no significant differences in preoperative function when comparing stiff aTSAs with stiff rTSAs. However, stiff rTSAs had significantly greater postoperative active and passive FE (p = 0.001 and 0.004, respectively), and active abduction (p = 0.001) compared with stiff aTSAs. The outcome scores were significantly more favourable in stiff rTSAs for the Shoulder Pain and Disability Index, Simple Shoulder Test, American Shoulder and Elbow Surgeons score, University of California, Los Angeles score, and the Constant score, compared with stiff aTSAs. When comparing the proportion of stiff aTSAs versus stiff rTSAs that exceeded the minimal clinically important difference and substantial clinical benefit, stiff rTSAs achieved both at greater rates for all measurements except active ER. The complication rate did not significantly differ between stiff aTSAs and stiff rTSAs, but there was a significantly higher rate of revision surgery in stiff aTSAs (p = 0.007). Conclusion. Postoperative overhead ROM, outcome scores, and rates of revision surgery favour the use of a rTSA rather than aTSA in patients with glenohumeral OA, an intact rotator cuff and limited FE, with similar rotational ROM in these two groups. Cite this article: Bone Joint J 2023;105-B(12):1303–1313

Aims. The objective of this systematic review was to describe trapeziectomy outcomes and complications in the context of osteoarthritis of the base of the thumb after a five-year minimum follow-up. Methods. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to guide study design, and 267 full-text articles were assessed for eligibility. After exclusion criteria application, 22 studies were included, involving 728 patients and 823 trapeziectomies. Outcomes included pre- and postoperative clinical and radiological characteristics. Complications and revisions were recorded. Results. All the studies reported good results regarding pain and range of motion at the last follow-up of 8.3 years (5 to 22); the mean satisfaction rate was 91% (84% to 100%). It was difficult to assess the impact on metacarpophalangeal joint motion in extension with contrary results. The key pinch returned to its preoperative values, whereas tip pinch showed a modest improvement (+14%), with a mild improvement found in grip strength (+25%) at the last follow-up. The mean progressive trapezial collapse was 48% (0% to 85%) and was not correlated with pain, grip strength, or satisfaction. The most represented complications were linked to tendons or nerves affected during additional procedures to stabilize the joint (11.6%; n = 56). Mechanical complications included symptomatic scapho-M1 impingement (3.1%; n = 15/580), leading to nine surgical revisions out of 581 trapeziectomies. Meta-analysis was not possible due to study heterogeneity and limited data. Conclusion. After a minimum five-year follow-up, trapeziectomy achieved high patient satisfaction and pain relief. However, strength seemed to be deteriorating with detrimental consequences, but this did not correlate with trapezial collapse. The issues related to underestimating mechanical complications and varying degrees of success should be highlighted in the information given to patients. Evidence-based analyses should help the surgeon in their decision-making. Cite this article: Bone Jt Open 2021;2(3):141–149

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