Three-dimensional motion analysis of pre- and postoperative thumb movement in trapeziometacarpal joint osteoarthritis-Comparison of arthrodesis and trapeziectomy with suspensionplasty.

Trapeziometacarpal osteoarthritis (TMC-OA) reduces the range of motion (ROM) of the thumb. However, the kinematic change achieved through surgical treatment remains unclear. Therefore, to quantify the kinematic change following TMC-OA surgery, we performed a three-dimensional motion analysis of the thumb using an optical motion capture system preoperatively and 1 year postoperatively in 23 patients with TMC-OA scheduled for arthrodesis (AD) or trapeziectomy with suspensionplasty (TS). Eighteen hands of nine healthy volunteers were also included as controls. Both procedures improved postoperative pain and Disability of the Arm, Shoulder and Hand scores, and AD increased pinch strength. The ROM of the base of the thumb was preserved in AD, which was thought to be due to the appearance of compensatory movements of adjacent joints even if the ROM of the TMC joint was lost. TS did not improve ROM. Quantifying thumb kinematic changes following TMC-OA surgery can improve our understanding of TMC-OA treatment and help select surgical procedures and postoperative assessment.

Three-Dimensional Printed Total Talus Replacement with a Concurrent Total Ankle Arthroplasty as a Personalized Approach for Advanced Ankle Osteoarthritis A Case Repor.

Ankle arthritis is becoming more common and can be pain-ful and debilitating. As the disease progresses, degenera-tive cystic changes may be found in the distal fibula, distal tibia, and talus. After failure of non-operative modalities, arthrodesis is often considered the surgical intervention of choice, but this leaves the patient with reduced range of motion, altered gait, and can negatively impact adjacent joints of the foot. Total ankle arthroplasty has been found to be an effective surgical option for ankle arthritis but is contraindicated in patients with talar collapse. When this is the case, a more personalized approach for preserving ankle motion is necessary. We present the case of a 65-year-old male with severe right ankle arthritis and talar collapse treated with a custom three-dimensionally printed talus and concurrent total ankle replacement with 2-year follow-up.

Reverse total shoulder arthroplasty for primary osteoarthritis with restricted preoperative forward elevation demonstrates similar outcomes but faster range of motion recovery compared to anatomic total shoulder arthroplasty.

BACKGROUND: Reverse total shoulder arthroplasty (RSA) has been increasingly utilized for a variety of shoulder pathologies that are difficult to treat with anatomical total shoulder arthroplasty (TSA). Few studies have compared the outcomes of TSA vs. RSA in patients with cuff intact glenohumeral osteoarthritis and poor preoperative forward elevation. This study aimed to determine whether there is a difference in functional outcomes and postoperative range of motion (ROM) between TSA and RSA in these patients. METHODS: This retrospective cohort study included 116 patients who underwent RSA or TSA between 2013 and 2022 for the treatment of rotator cuff intact primary osteoarthritis with restricted preoperative forward flexion (FF) and a minimum 1-year follow-up. Each arthroplasty group was divided into 2 subgroups: patients with preoperative FF between 91° and 120° or FF lower than or equal to 90°. Patients' clinical outcomes, including active ROM, American Shoulder and Elbow Surgeons score, visual analog scale for pain, and subjective shoulder value were collected. Clinical and radiographic complications were evaluated. RESULTS: There was no significant difference between RSA and TSA in terms of sex (58.3% male vs. 62.2% male, P = .692), or follow-up duration (20.1 months vs. 17.7 months, P = .230). However, the RSA cohort was significantly older (72.0 ± 8.2 vs. 65.4 ± 10.6, P = .012) and weaker in FF and (ER) before surgery (P < .001). There was no difference between RSA (57 patients) and TSA (59 patients) in visual analog scale pain score (1.2 ± 2.3 vs. 1.3 ± 2.3, P = .925), subjective shoulder value score (90 ± 15 vs. 90 ± 15, P = .859), or American Shoulder and Elbow Surgeons score (78.4 ± 20.5 vs. 82.1 ± 23.2, P = .476). Postoperative active ROM was statistically similar between RSA and TSA cohorts in FF (145 ± 26 vs. 146 ± 23, P = .728) and ER (39 ± 15 vs. 41 ± 15, P = .584). However, internal rotation was lower in the RSA cohort (P < .001). This was also true in each subgroup. RSA led to faster postoperative FF and ER achievement at 3 months (P < .001). There was no statistically significant difference in complication rates between cohorts. CONCLUSION: This study demonstrates that patients with glenohumeral osteoarthritis who have a structurally intact rotator cuff but limited preoperative forward elevation can achieve predictable clinical improvement in pain, ROM, and function after either TSA or RSA. Reverse arthroplasty may be a reliable treatment option in patients at risk for developing rotator cuff failure.

Effects of Immobilization and Swimming on the Progression of Osteoarthritis in Mice.

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration of articular cartilage and thickening and sclerosis of the subchondral bone. Mechanical factors play significant roles in the development and progression of OA, but it is still controversial whether exercise or rest is a more effective treatment for OA patients. In this study, we compared the effects of swimming and immobilization at different stages of OA in mice. Four weeks (the middle stage of OA) or eight weeks (the late stage of OA) after DMM (destabilization of the medial meniscus) surgery, the mice were subjected to four-week immobilization or swimming. Ink blot analysis and a beam walking test were performed to measure the gait and balance ability. Histological analysis was performed to determine the trabecular bone area, the thickness of subchondral bone, the thickness of the cartilage, the OARSI score, and the expression of MMP13 (matrix metalloproteinases) and IL-6 (interleukin). The results showed that at the middle stage of OA, both immobilization and swimming slowed down the progression of OA. Immobilization relieved OA to a certain extent by decreasing the production of regulatory factors to attenuate the degeneration of cartilage, which partly relieved the effects of DMM on gait, mainly in the hindlimb. Swimming mainly attenuated the thickening and rescued the area of subchondral bone.

Radiographic Severity May Not be Associated with Pain and Function in Glenohumeral Arthritis.

BACKGROUND: Despite the routine use of plain radiographs to stratify the severity of glenohumeral osteoarthritis, little is known about the relationship between radiographic measures and patient-perceived pain and function. QUESTIONS/PURPOSES: (1) What radiographic findings are associated with worse pain and function in patients with glenohumeral osteoarthritis? (2) What demographic factors are associated with worse pain and function in patients with glenohumeral osteoarthritis? METHODS: This retrospective study included patients presenting for an initial office visit for primary glenohumeral osteoarthritis. Patients with other concurrent shoulder pathologic findings, prior surgery, lack of pain and functional scores, recent injection, or inadequate radiographs were excluded. Between January 2017 and January 2019, 3133 patients were eligible based on these inclusion criteria; 59% (1860) had outcome assessments and 48% (893) of those had radiographs. An additional 42% (378) of those with radiographs were excluded because of other shoulder findings, recent injection, prior surgery, or inadequate radiographs, leaving 16% (515 of 3133) who were fully analyzed in this study. A radiographic review included the joint space width, posterior humeral head subluxation, inferior humeral head osteophyte size, cystic change, and head asphericity. Additionally, radiographic arthritis was classified according to the Walch, Samilson-Prieto, and Kellgren-Lawrence classifications by two separate reviewers. Radiographic and demographic criteria as well as the presence of psychologic or mental illness were correlated with VAS Pain (range 1-10; minimal clinically important difference [MCID] 1.6), American Shoulder and Elbow Surgeons (ASES; range 0-100; MCID 13.6), Single Assessment Numeric Evaluation (SANE; range 0-100; MCID 14), and Simple Shoulder Test (SST; range 0-12; MCID 1.5) scores using univariate and multivariable regression analyses. RESULTS: After accounting for age, gender, and psychologic illness in the multivariable analysis, we found that patients with Samilson-Prieto Grade 4 arthrosis had lower VAS Pain scores (ß = -1.9; p = 0.02) than those with Grade 0 or 1 did; however, no clinically important associations were found between Samilson-Prieto Grade 4 and ASES (ß = 7; p = 0.25), SANE (ß = 4; p = 0.63), or SST (ß = 0.5; p = 0.62) scores. No clinically important associations were found between Kellgren-Lawrence Grade 3 and VAS Pain (ß = 1.4; p = 0.10), ASES (ß = -8; p = 0.22), SANE (ß = -13; p = 0.11), or SST scores (ß = 0.4; p = 0.66). Radiographic joint space and posterior subluxation also did not have any clinically important associations with VAS Pain or functional scores. In assessing Walch glenoid type, there was no clinically important association between glenoid type and VAS Pain (F = 3.1; p < 0.01), ASES (F = 1.9; p = 0.15), SANE (F = 0.45; p = 0.66), or SST scores (F = 0.76; p = 0.71). Men had higher SST scores than women did (ß = 2.0; p < 0.01), but there were no clinically important differences in VAS Pain (ß = -0.4; p = 0.04), ASES (ß = 6; p < 0.01), or SANE (ß = 4; p = 0.07) scores. No clinically important association was found between age or the presence of any psychologic illness and VAS Pain or functional scores. CONCLUSION: In patients with glenohumeral arthritis, no consistent clinically important differences in pain or function were discovered with respect to radiographic or demographic factors. Surgeons should understand that the pain levels of patients with glenohumeral arthritis may not parallel radiographic severity. Future studies can build on these findings by examining other non-radiographic or demographic factors that affect pain in patients with shoulder arthritis, such as psychological factors. LEVEL OF EVIDENCE: Level III, prognostic study.

Regulation of osteoarthritis development by ADAM17/Tace in articular cartilage.

INTRODUCTION: A disintegrin and metalloproteinase 17 (Adam17), also known as TNFα-converting enzyme (Tace), is a membrane-anchored protein involved in shedding of TNF, IL-6 receptor, ligands of epidermal growth factor receptor (EGFR), and Notch receptor. This study aimed to examine the role of Adam17 in adult articular cartilage and osteoarthritis (OA) pathophysiology. MATERIALS AND METHODS: Adam17 expression was examined in mouse knee joints during OA development. We analyzed OA development in tamoxifen-inducible chondrocyte-specific Adam17 knockout mice of a resection of the medial meniscus and medial collateral ligament (medial) model, destabilization of the medial meniscus (DMM) model, and aging model. We analyzed downstream pathways by in vitro experiments, and further performed intra-articular administration of an Adam17 inhibitor TAPI-0 for surgically induced mouse OA. RESULTS: Adam17 expression in mouse articular cartilage was increased by OA progression. In all models, Adam17 knockout mice showed ameliorated progression of articular cartilage degradation. Adam17 knockout decreased matrix metallopeptidase 13 (Mmp13) expression in both in vivo and in vitro experiments, whereas Adam17 activation by phorbol-12-myristate-13-acetate (PMA) increased Mmp13 and decreased aggrecan in mouse primary chondrocytes. Adam17 activation enhanced release of soluble TNF and transforming growth factor alpha, a representative EGF ligand, from mouse primary chondrocytes, while it did not change release of soluble IL-6 receptor or nuclear translocation of Notch1 intercellular domain. Intra-articular administration of the Adam17 inhibitor ameliorated OA progression. CONCLUSIONS: This study demonstrates regulation of OA development by Adam17, involvement of EGFR and TNF pathways, and the possibility of Adam17 as a therapeutic target for OA.

The risk of revision following total hip arthroplasty in patients with inflammatory bowel disease, a registry based study.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestinal tract and is associated with decreased bone mineral density. IBD patients are at higher risk of osteopenia, osteoporosis and fracture compared to non-IBD patients. The impact of IBD on the performance of orthopedic implants has not been well studied. We hypothesized that a history of IBD at the time of primary total hip arthroplasty (THA) would increase the risk of subsequent failure as assessed by revision surgery. A retrospective implant survival analysis was completed using the Swedish Hip Arthroplasty Registry and the Sweden National Patient Register. A total of 150,073 patients undergoing THA for osteoarthritis within an 18-year period were included in the study. THA patients with (n = 2,604) and without (n = 147,469) a history of IBD at the time of THA were compared with primary revision as the main endpoint and adjusted using sex, age category and comorbidity (Elixhauser scores) as covariates. We found that patients with a history of IBD had a relatively higher risk of revision surgery for septic causes while the non-IBD patients had a relatively higher risk of revision for aseptic causes (p = 0.004). Our findings suggest there may be an association between gut health and THA performance.

Enhancement of DUSP14 (dual specificity phosphatase 14) limits osteoarthritis progression by alleviating chondrocyte injury, inflammation and metabolic homeostasis.

Osteoarthritis (OA) is a proverbial inflammatory degenerative joint disease associated with the acceleration of the aging process and is characterized by chondrocyte injury and articular cartilage degradation. Dual-specificity phosphatase 14 (Dusp14), a common member of the DUSP family, has been implicated in multiple inflammatory diseases and bone loss. Nevertheless, the function of DUSP14 in OA remains unclear. In the present study, down-regulation of DUSP14 was corroborated in anterior cruciate ligament transection (ACLT)-induced OA rats and interleukin-1ß (IL-1ß)-stimulated chondrocytes. Additionally, the gain of DUSP14 reversed IL-1ß-induced inhibition of chondrocyte viability but attenuated cell apoptosis. Concomitantly, DUSP14 overexpression muted IL-1ß-induced release of pro-inflammatory mediators NO and prostaglandin E2 (PGE2), as well as pro-inflammatory cytokine levels (IL-6 and TNF-α). Furthermore, up-regulation of DUSP14 overturned the effects of IL-1ß on the inhibition of collagen II and aggrecan expression, and enhancement of A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS5) and matrix metalloproteinases (MMPs; MMP3 and MMP-13). Mechanistically, DUSP14 elevation increased the p-Adenosine 5'-monophosphate-activated protein activated protein kinase(AMPK), inhibitor of NF-κB (IκB) expression and decreased p-p65 NF-κB expression, indicating that DUSP14 might restore the AMPK-IκB pathway to restrain NF-κB signaling under IL-1ß exposure. Notably, blockage of AMPK signaling muted the protective efficacy of DUSP14 elevation against IL-1ß-induced inflammatory injury and metabolism disturbance in chondrocytes. Interestingly, histological evaluation substantiated that DUSP14 injection alleviated cartilage degradation in OA rats. Together, DUSP14 may ameliorate OA progression by affecting chondrocyte injury, inflammatory response and cartilage metabolism homeostasis, implying a promising therapeutic strategy against OA.

Update on Thumb Basal Joint Arthritis Surgery.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Comprehend anatomy and biomechanics of the normal and arthritic trapeziometacarpal joint. 2. Evaluate best evidence for diagnosis and for operative and nonoperative treatment of thumb osteoarthritis. 3. Understand treatment pitfalls of basilar joint arthritis and complication avoidance. SUMMARY: Articular and ligamentous anatomy of the trapeziometacarpal joint enables complex motions. Disability from arthritis, common at the trapeziometacarpal joint, is debilitating. Furthering the understanding of how trapeziometacarpal arthritis develops can improve treatment. The authors provide current best evidence for diagnosis and treatment of basilar joint arthritis. Pitfalls in treatment are discussed.

Studies on the Role of circRNAs in Osteoarthritis.

OBJECTIVE: Provide a reference to elucidate the mechanism of circRNAs regulating osteoarthritis (OA) and the clinical treatment. METHODS: Herein, articles about circRNAs (hsa-circ) and osteoarthritis in the recent 5 years have been reviewed and the differential expression and regulatory effect of circRNAs in OA deduced. Based on these conclusions and Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the acquired circRNAs, the potential functions and interactions of circRNAs in OA and the involved signaling pathways are discussed. RESULTS: A total of 33 studies meeting the inclusion criteria were included in this study, and 27 circRNAs were upregulated and 8 circRNAs were downregulated in OA. A total of 31 circRNAs were finally included in the PPI, GO, and KEGG analyses. From PPI, 12 map nodes and 7 map edges were interrelated. VWF had the biggest node and edge size. From GO, VWF showed a majority of the functions. From KEGG, circRNAs are enriched in PI3K/AKT, human papillomavirus infection (HPI), and focal adhesion (FA) pathways, and VWF was involved in major pathways. CONCLUSION: We found that most articles about circRNAs regulating OA in the recent 5 years focused on the mechanism, especially the absorption effect of circ-miRNA as sponges in the recent 2 years, while most of the articles about their functions addressed ECM and PI3K, AKT, and mTOR signaling pathways. Future studies might focus on the functions of circRNAs, and circRNA VWF, with preferable functions, interactions, and involvement, can be used as a biological indicator to detect OA in clinical practice.

Extracellular vesicles as novel approaches for the treatment of osteoarthritis: a narrative review on potential mechanisms.

Osteoarthritis (OA) is a progressive degeneration of articular cartilage with involvement of synovial membrane, and subchondral bone. Current treatment approaches have focused on controlling the OA symptoms, pain, and inflammation. Recently, cell-based therapies, including the application of stem cells such as mesenchymal stem cells (MSCs), have been introduced for restoration of the articular cartilage. Despite promising outcomes, there are some limitations in the application of MSCs for OA treatment. It has been demonstrated that the regenerative potential of stem cells is related to the production of paracrine factors. Extracellular vehicles (EVs), the main component of cell secretome, are membrane-bounded structures that deliver biologically active agents. The delivery of molecules (e.g., nucleic acids, proteins, and lipids) leads to cell-to-cell communication and the alteration of cell functions. In this review, general characteristics of EVs, as well as their potential mechanisms in the prevention and treatment of OA were considered. Based on in vitro and in vivo studies, EVs have shown to contribute to cartilage regeneration via suppression of degenerative factors and regulation of chondrocyte function in the synthesis of extracellular matrix components. Also, they inhibit the progression of OA or protect the cartilage from degradation via their impact on inflammatory cytokines. The different signaling pathways of EVs against the pathologic features of OA were summarized in this review. According to the results obtained from several investigations, more investigations should be design to prove the safety and effectiveness of EVs in the treatment and prevention of OA progression.

Thumb Carpometacarpal Arthritis Surgery: The Patient Experience.

BACKGROUND: Patients with symptomatic recalcitrant thumb carpometacarpal arthritis often undergo surgery. Although most surgical patients do well, the authors anticipated that a substantial portion of their thumb carpometacarpal surgery patients would have unsatisfactory experiences and express unmet expectations, dissatisfaction, and regret, regardless of surgical procedure performed. The authors hypothesized those experiences would correlate with patient-reported outcomes scores. METHODS: The authors identified patients who had undergone trapeziectomy alone or with ligament reconstruction 1 to 4 years previously for primary thumb carpometacarpal arthritis. One hundred twelve patients completed Quick Disabilities of the Arm, Shoulder and Hand and visual analogue scale pain, expectations, satisfaction, and regret questionnaires. RESULTS: More than 40 percent of patients expected to "return to normal" after surgery for pain, strength, and/or function. Including all patients, 7, 19, and 11 percent had unmet expectations for improvement in pain, strength, and function, respectively. Twelve percent expressed dissatisfaction with their outcome. Although just 4 percent regretted undergoing surgery, 13 percent would likely not recommend the procedure to someone they care about. There were no statistically significant differences for any patient-reported outcomes between trapeziectomy-alone (n = 20) and trapeziectomy with ligament reconstruction (n = 92). Visual analogue scale and Quick Disabilities of the Arm, Shoulder and Hand questionnaire scores were both moderately correlated with expectations being met for pain, strength, and function and for satisfaction with surgical outcome. CONCLUSIONS: Patients' thumb carpometacarpal surgical experiences vary considerably. Many express dissatisfaction or a lack of expectations met with the two most common procedures. A thorough understanding and review of expectations preoperatively may be uniquely pertinent for these patients. Further research should determine predictors and potentially modifiable factors for unsatisfactory outcomes.

Exploration of biomarkers in osteoarthritis based on bioinformatics.

ABSTRACT: Osteoarthritis (OA) seriously affects human health and brings a heavy social burden. This study aimed to identify new biomarkers involved in OA. Differential expression analysis and gene set enrichment analysis were performed on the microarray data set of OA. Identify key genes from immune-related DEGs and verify their expression in the validation set. CIBERSORT was used to analyze the infiltration of immune cells. The correlation between key genes and immune cells were conducted. A total of 1779 DEGs were identified in GSE82107. Gene set enrichment analysis results of top 4 for hallmark revealed the enrichment of DEGs were associated with genes in "HALLMARK_TNFA_SIGNALING_VIA_NFKB", "HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION", "HALLMARK_INFLAMMATORY_RESPONSE" and "HALLMARK_HYPOXIA". A total of 108 immune-related DEGs were identified from the overlap between 2498 immune-related genes and 1779 DEGs. The expression of top 6 immune-related DEGs including ADIPOQ, FABP4, FOS, IGLC1, IGLV1-44 and leptin were measured in the validation set, the results shown that IGLC1 and IGLV1-44 might play a key role in the synovial membrane of OA. A total of 8 kinds of cells including B cells memory, Plasma cells, T cells CD4 memory resting, T cells gamma delta, natural killer cells activated, macrophages M0, Mast cells resting and Mast cells activated have significant differences in infiltration between the OA group and the control group. Besides, the expressions of IGLC1 and IGLV1-44 are highly correlated. Our results indicated that IGLC1 and IGLV1-44 may play the role of immune-related biomarkers in OA.

The role of renin angiotensin system in the pathophysiology of rheumatoid arthritis.

BACKGROUND: In rheumatoid arthritis (RA) and osteoarthritis (OA), chronic inflammatory processes lead to progresive joint destruction. The renin-angiotensin system (RAS) is involved in the pathogenesis of RA and OA. The aim of this mini-review article is to summarize evidence on the role of RAS in RA and OA. METHODS: A non-systematic search in Pubmed included terms as "rheumatoid arthritis", "renin angiotensin system", "osteopenia", "RANKL", "DKK-1", "MMP", "inflammation", "angiogenesis", "local renin-angiotensin system", "angiotensin converting enzyme", "AT2 receptor", "Ang-(1-7)", "VEGF", "angiotensine receptor blocker", "angiotensin converting enzyme inhibitors", "renin inhibitors". RESULTS: Both RAS axes, the classical one, formed by angiotensin converting enzyme (ACE), angiotensin (Ang) II and AT1 receptor (AT1R) and the counter-regulatory one, composed by ACE2, Ang-(1-7) and the Mas receptor, modulate inflammation and tissue damage. Ang II activates pro-inflammatory mediators and oxidative stress. Conversely, Ang-(1-7) exerts anti-inflammatory actions, decreasing cytokine release, leukocyte attraction, density of vessels, tissue damage and fibrosis. Angiogenesis facilitates inflammatory cells invasion, while osteopenia causes joint dysfunction. Up-regulated osteoclastogenisis and down-regulated osteoblastogeneses were associaed with the activation of the classical RAS axis. Three different pathways, RANKL, DKK-1 and MMPs are enhanced by classical RAS activation. The treatment of RA included methotrexate and corticosteroids, which can cause side effects. Studies with angiotensin receptor blockers (ARBs), angiotensin converting enzyme inhibitors (ACEi) and renin inhibitors have been conducted in experimental and clinical RA with promising results. CONCLUSION: The classical RAS activation is an important mechanism in RA pathogenesis and the benefit of ARB and ACEi administration should be further investigated.

Pathology-pain relationships in different osteoarthritis animal model phenotypes: it matters what you measure, when you measure, and how you got there.

OBJECTIVE: To determine whether osteoarthritis (OA) pain characteristics and mechanistic pathways in pre-clinical models are phenotype-specific. DESIGN: Male 11-week-old C57BL6 mice had unilateral medial-meniscal-destabilization (DMM) or antigen-induced-arthritis (AIA), vs sham-surgery/immunised-controls (Sham/Im-CT). Pain behaviour (allodynia, mechanical- and thermal-hyperalgesia, hindlimb static weight-bearing, stride-length) and lumbar dorsal root ganglia (DRG) gene-expression were measured at baseline, day-3, week-1/-2/-4/-8/-16, and pain-behaviour:gene-expression:joint-pathology associations investigated. RESULTS: DMM and AIA induced structural OA defined by progressively increasing cartilage erosion, subchondral bone sclerosis and osteophyte size and maturation. All pain-behaviours were modified, with model-specific differences in severity and temporal pattern. Tactile allodynia developed acutely in both models and persisted to week-16. During early-OA (wk4-8) there was; reduced right hindlimb weight-bearing in AIA; thermal-hyperalgesia and reduced stride-length in DMM. During chronic-OA (wk12-16); mechanical-hyperalgesia and reduced right hindlimb weight-bearing were observed in DMM only. There were no associations in either model between different pain-behaviour outcomes. A coordinated DRG-expression profile was observed in sham and Im-CT for all 11 genes tested, but not in AIA and DMM. At wk-16 despite equivalent joint pathology, changes in DRG-expression (Calca, Trpa1, Trpv1, Trpv4) were observed only in DMM. In AIA mechanical-hyperalgesia was associated with Trpv1 (r = -0.79) and Il1b (r = 0.53). In DMM stride-length was associated with Calca, Tac1, Trpv1, Trpv2, Trpv4 and Adamts5 (r = 0.4-0.57). DRG gene-expression change was correlated with subchondral-bone sclerosis in DMM, and cartilage damage in AIA. Positive pain-behaviour:joint-pathology associations were only present in AIA - for synovitis, subchondral-bone resorption, chondrocyte-hypertrophy and cartilage damage. CONCLUSION: Pain and peripheral sensory neuronal responses are OA-phenotype-specific with distinct pathology:pain-outcome:molecular-mechanism relationships.

Tyrosine kinases regulate chondrocyte hypertrophy: promising drug targets for Osteoarthritis.

Osteoarthritis (OA) is a major health problem worldwide that affects the joints and causes severe disability. It is characterized by pain and low-grade inflammation. However, the exact pathogenesis remains unknown and the therapeutic options are limited. In OA articular chondrocytes undergo a phenotypic transition becoming hypertrophic, which leads to cartilage damage, aggravating the disease. Therefore, a therapeutic agent inhibiting hypertrophy would be a promising disease-modifying drug. The therapeutic use of tyrosine kinase inhibitors has been mainly focused on oncology, but the Food and Drug Administration (FDA) approval of the Janus kinase inhibitor Tofacitinib in Rheumatoid Arthritis has broadened the applicability of these compounds to other diseases. Interestingly, tyrosine kinases have been associated with chondrocyte hypertrophy. In this review, we discuss the experimental evidence that implicates specific tyrosine kinases in signaling pathways promoting chondrocyte hypertrophy, highlighting their potential as therapeutic targets for OA.

Curcumin Attenuates Environment-Derived Osteoarthritis by Sox9/NF-kB Signaling Axis.

Inflammation has a fundamental impact on the pathophysiology of osteoarthritis (OA), a common form of degenerative arthritis. It has previously been established that curcumin, a component of turmeric (Curcuma longa), has anti-inflammatory properties. This research evaluates the potentials of curcumin on the pathophysiology of OA in vitro. To explore the anti-inflammatory efficacy of curcumin in an inflamed joint, an osteoarthritic environment (OA-EN) model consisting of fibroblasts, T-lymphocytes, 3D-chondrocytes is constructed and co-incubated with TNF-α, antisense oligonucleotides targeting NF-kB (ASO-NF-kB), or an IkB-kinase (IKK) inhibitor (BMS-345541). Our results show that OA-EN, similar to TNF-α, suppresses chondrocyte viability, which is accompanied by a significant decrease in cartilage-specific proteins (collagen II, CSPG, Sox9) and an increase in NF-kB-driven gene proteins participating in inflammation, apoptosis, and breakdown (NF-kB, MMP-9, Cox-2, Caspase-3). Conversely, similar to knockdown of NF-kB at the mRNA level or at the IKK level, curcumin suppresses NF-kB activation, NF-kB-promotes gene proteins derived from the OA-EN, and stimulates collagen II, CSPG, and Sox9 expression. Furthermore, co-immunoprecipitation assay shows that curcumin reduces OA-EN-mediated inflammation and chondrocyte apoptosis, with concomitant chondroprotective effects, due to modulation of Sox-9/NF-kB signaling axis. Finally, curcumin selectively hinders the interaction of p-NF-kB-p65 directly with DNA-this association is disrupted through DTT. These results suggest that curcumin suppresses inflammation in OA-EN via modulating NF-kB-Sox9 coupling and is essential for maintaining homeostasis in OA by balancing chondrocyte survival and inflammatory responses. This may contribute to the alternative treatment of OA with respect to the efficacy of curcumin.

Frontier review of the roles of exosomes in osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease; however, its exact pathophysiology and early diagnosis are still a challenge. Growing attention to the exosomes may inspire innovations that would make the current management of OA more effective. The exosomes in synovial fluid are relatively stable, and they can be easily isolated by the relatively noninvasive procedure of liquid biopsy to provide diagnostic and monitoring value. Some miRNAs (miR-504, miR-146a, miR-26a, miR-200c, and miR-210) have been known to be secreted in exosomes of OA patients. On the other hand, intraarticular injection of platelet-rich plasma (PRP) is becoming a popular therapy for OA patients. PRP is also a source of exosomes and their numerous contents. It is evident from the literature that PRP-derived exosomes can induce chondrogenic gene expression in OA chondrocytes. Here, we review the latest findings on the roles of exosomes in OA with the emphasis on PRP-derived exosomes and their potential applications for treating OA.

Validity and Reliability of the Turkish Version of Western Ontario Osteoarthritis of the Shoulder Index.

OBJECTIVES: This study aims to adapt the Western Ontario Osteoarthritis of the Shoulder (WOOS) index specific to shoulder osteoarthritis into Turkish and to evaluate its validity and reliability. PATIENTS AND METHODS: The WOOS index was translated and culturally adapted into Turkish, systematically. It was applied to a total of 68 patients (17 males, 51 females; mean age: 61.5±8.7 years; range, 45 to 80 years) with osteoarthritis of the shoulder treated conservatively. The reliability of the scale was checked through internal consistency and test-retest methods. Internal consistency was analyzed with Cronbach alpha value. Test-retest reliability was assessed using an intraclass correlation coefficient (ICC) with 25 patients. The Western Ontario Rotator Cuff (WORC), the Shoulder Pain and Disability Index (SPADI), and the Society of American Shoulder and Elbow Surgeons Standardized Shoulder Assessment (ASES) scores were used to conduct concurrent validity. RESULTS: The Cronbach alpha value of the scale was found to be excellent as 0.92 (p<0.001). The ICC value was also excellent as 0.97 (p<0.001). There was an excellent positive correlation with WORC (0.847; p<0.001) and a very good positive correlation with SPADI (0.788; p<0.001). It was also negatively very good to correlate with the ASES (-0.754; p<0.001). Additionally, subsections of WOOS had a good correlation with the corresponding subsections of WORC (0.779-0.664; p<0.001). CONCLUSION: The Turkish version of the WOOS index is a valid and reliable tool and is recommended for use in the assessment of patients with osteoarthritis of the shoulder.