Patient-Experience of Trapeziectomy for Trapeziometacarpal Osteoarthritis in Wide-Awake Local Anesthesia no Tourniquet, 2-Year Follow-up.

PURPOSE OF THE STUDY: The purpose of this study was to assess the patient experience of trapeziectomy under WALANT for trapeziometacarpal joint (TMJ) osteoarthritis (OA) in a prospective study with 2-year follow-up. MATERIAL AND METHODS: The study included 23 patients with TMJ OA undergoing trapeziectomy with WALANT. All patients were seen by a hand therapist preoperatively and at 3, 12, and 24 months postoperatively. At each visit, VAS pain scores, thumb range of motion, grip strength, and Disabilities of the Arm, Shoulder and Hand (DASH) score were assessed. The Picker Patient Experience (PPE-15) questionnaire was administered within 2 weeks of surgery. RESULTS: All 23 patients completed the PPE-15 questionnaire. Their mean age was 64 years. The 21 patients who remained at the 24-month follow-up all said they would choose the same anaesthesia method again. At this follow-up, VAS pain scores, thumb range of motion, key pinch grip and DASH scores had improved significantly, while thumb opposition and hand grip strength remained largely unchanged. The majority of patients felt well informed before and during the procedure, and all patients rated pain relief as good or satisfactory. Nearly 40% of patients reported receiving inadequate information about the postoperative medications. DISCUSSION: Patients have a positive attitude to trapeziectomy with WALANT, and seem to prefer WALANT over other methods of anaesthesia. Trapeziectomy with WALANT for TMJ OA is a safe procedure and appears to give a functional outcome similar to trapeziectomy under general anaesthesia. CONCLUSIONS: Trapeziectomy with WALANT for TMJ OA is safe, preferred by patients and has similar clinical outcome as trapeziectomy in general anesthesia. KEY WORDS: trapeziectomy, osteoarthritis, WALANT.

Functional Nanomaterials for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease, affecting more than 595 million people worldwide. Nanomaterials possess superior physicochemical properties and can influence pathological processes due to their unique structural features, such as size, surface interface, and photoelectromagnetic thermal effects. Unlike traditional OA treatments, which suffer from short half-life, low stability, poor bioavailability, and high systemic toxicity, nanotherapeutic strategies for OA offer longer half-life, enhanced targeting, improved bioavailability, and reduced systemic toxicity. These advantages effectively address the limitations of traditional therapies. This review aims to inspire researchers to develop more multifunctional nanomaterials and promote their practical application in OA treatment.

Cost of lost productivity in inflammatory arthritis and osteoarthritis in the year before and after diagnosis: An inception cohort study.

AIM: Existing studies on the cost of inflammatory arthritis (IA) and osteoarthritis (OA) are often cross-sectional and/or involve patients with various disease durations, thus not providing a comprehensive perspective on the cost of illness from the time of diagnosis. In this study, we therefore assessed the cost of lost productivity in an inception cohort of patients with IA and OA in the year before and after diagnosis. METHODS: Employment status, monthly income, days absent from work, and presenteeism were collected at diagnosis and 1 year later to estimate the annual costs of unemployment, absenteeism, and presenteeism using human capital approach. Non-parametric bootstrapping was performed to account for the uncertainty of the estimated costs. RESULTS: Compared to patients with OA (n = 64), patients with IA (n = 102, including 48 rheumatoid arthritis, 19 spondyloarthritis, 23 psoriatic arthritis, and 12 seronegative IA patients) were younger (mean age: 52.3 vs. 59.5 years) with a greater proportion receiving treatment (99.0% vs. 67.2%) and a greater decrease in presenteeism score (median: 15% vs 10%) 1 year after diagnosis. Annual costs of absenteeism and presenteeism were lower in patients with IA than those with OA both in the year before (USD566 vs. USD733 and USD8,472 vs. USD10,684, respectively) and after diagnosis (USD636 vs. USD1,035 and USD6,866 vs. USD9,362, respectively). CONCLUSION: Both IA and OA impose substantial cost of lost productivity in the year before and after diagnosis. The greater improvement in productivity seen in patients with IA suggests that treatment for IA improves work productivity.

Anthropometric study of the scapula in a contemporary population from granada. Sex estimation and glenohumeral osteoarthritis prevalence.

Anthropometric studies of the scapula have been rare in Spanish populations, nevertheless they are of current interest in forensic anthropology for estimation of sex. Although the estimation of sex is usually carried out on the pelvis and skull, other measurements related to the scapula can be helpful when the skeletal remains are incomplete. Glenohumeral osteoarthritis development is influenced, among others, by the morphology of the scapula, which is one of the less studied aspects. We carried out a descriptive study of anthropometric parameters in a series of 157 scapulae (82 individuals) on bone remains dated to the 20th century from a population of Granada (Southern Spain). Seventy seven (49%) were right-side and 80 (51%) left-side; 72 (45.9%) were from males and 85 (54.1%) from females, and the mean age at death was 70.76±11.7 years. The objective was to develop a discrimination function for sex estimation based on anthropometric parameters of the scapula other than those considered to date, and to analyze the prevalence of glenohumeral osteoarthritis in relation to selected anthropometric parameters. A logistic regression model based on parameters of the upper-external segment of the scapula was done. The obtained formula: 1/1+e^ (- (-57.911 + 0.350*B + 0283*C + 0.249*b + 0.166*a +-0.100*ß) classifies male sex with 98.3% accuracy and female sex with 92.1%. Glenohumeral osteoarthritis was detected in 16.6% of individuals and was related to age (p<0.05), scapular length (p<0.05), glenoid width (p<0.05), glenopolar angle (p<0.05), and α angle (p<0.05) in bivariate analyses but showed no significant associations in multivariate analyses. This approach can be useful for anthropological-forensic identification when scapula remains are incomplete. Glenohumeral osteoarthritis is significantly associated with a smaller α angle.

Updates in the skeletal and joint protective effects of tocotrienol: a mini review.

Osteoporosis and osteoarthritis continue to pose significant challenges to the aging population, with limited preventive options and pharmacological treatments often accompanied by side effects. Amidst ongoing efforts to discover new therapeutic agents, tocotrienols (TTs) have emerged as potential candidates. Derived from annatto bean and palm oil, TTs have demonstrated efficacy in improving skeletal and joint health in numerous animal models of bone loss and osteoarthritis. Mechanistic studies suggest that TTs exert their effects through antioxidant, anti-inflammatory, Wnt-suppressive, and mevalonate-modulating mechanisms in bone, as well as through self-repair mechanisms in chondrocytes. However, human clinical trials in this field remain scarce. In conclusion, TTs hold promise as agents for preventing osteoporosis and osteoarthritis, pending further evidence from human clinical trials.

A smart hypochlorous acid fluorescent probe enabling Ibuprofen-release for osteoarthritis theranostics.

Background: Osteoarthritis (OA) standing as the most prevalent form of arthritis, closely associates with heightened levels of reactive oxygen species, particularly hypochlorous acid (HOCl). Although there are numerous probes available for detecting HOCl in the OA region, probes with dual functions of diagnostic and therapeutic capabilities are still significantly lacking. While this type of probe can reduce the time gap between diagnosis and treatment, which is clinically needed. Methods: We developed a fluorescent probe (DHU-CBA1) toward HOCl with theranostics functions through the release of methylene blue (MB) and ibuprofen (IBP) in this work. DHU-CBA1 can detect HOCl with high specificity and sensitivity, releasing MB and IBP with an impressive efficiency of ≥ 95% in vitro. Results: DHU-CBA1 exhibits good biosafety, enabling in vivo imaging of endogenous HOCl, along with reducing arthritis scores, improving synovitis and cartilage damage, and maintaining catabolic balance while alleviating senescence in cartilage. Conclusions: This study proposes a novel approach to enhance osteoarthritis therapy by releasing IBP via a smart HOCl-enabled fluorescent probe.

Cinnamaldehyde-Treated Bone Marrow Mesenchymal-Stem-Cell-Derived Exosomes via Aqueous Two-Phase System Attenuate IL-1ß-Induced Inflammation and Catabolism via Modulation of Proinflammatory Signaling Pathways.

Osteoarthritis (OA) is a degenerative joint disorder that is distinguished by inflammation and chronic cartilage damage. Interleukin-1ß (IL-1ß) is a proinflammatory cytokine that plays an important role in the catabolic processes that underlie the pathogenesis of OA. In this study, we investigate the therapeutic efficacy of exosomes derived from untreated bone-marrow-derived mesenchymal stem cells (BMMSC-Exo) and those treated with cinnamaldehyde (BMMSC-CA-Exo) for preventing the in vitro catabolic effects of IL-1ß on chondrocytes. We stimulated chondrocytes with IL-1ß to mimic the inflammatory microenvironment of OA. We then treated these chondrocytes with BMMSC-Exo and BMMSC-CA-Exo isolated via an aqueous two-phase system and evaluated their effects on the key cellular processes using molecular techniques. Our findings revealed that treatment with BMMSC-Exo reduces the catabolic effects of IL-1ß on chondrocytes and alleviates inflammation. However, further studies directly comparing treatments with BMMSC-Exo and BMMSC-CA-Exo are needed to determine if CA preconditioning can provide additional anti-inflammatory benefits to the exosomes beyond those of CA preconditioning or treatment with regular BMMSC-Exo. Through a comprehensive molecular analysis, we elucidated the regulatory mechanisms underlying this protective effect. We found a significant downregulation of proinflammatory signaling pathways in exosome-infected chondrocytes, suggesting the potential modulation of the NF-κB and MAPK signaling cascades. Furthermore, our study identified the molecular cargo of BMMSC-Exo and BMMSC-CA-Exo, determining the key molecules, such as anti-inflammatory cytokines and cartilage-associated factors, that may contribute to their acquisition of chondroprotective properties. In summary, BMMSC-Exo and BMMSC-CA-Exo exhibit the potential as therapeutic agents for OA by antagonizing the in vitro catabolic effects of IL-1ß on chondrocytes. The regulation of the proinflammatory signaling pathways and bioactive molecules delivered by the exosomes suggests a multifaceted mechanism of action. These findings highlight the need for further investigation into exosome-based therapies for OA and joint-related diseases.

Quercetin Modulates Ferroptosis via the SIRT1/Nrf-2/HO-1 Pathway and Attenuates Cartilage Destruction in an Osteoarthritis Rat Model.

Osteoarthritis (OA) is the most common joint disease, causing symptoms such as joint pain, swelling, and deformity, which severely affect patients' quality of life. Despite advances in medical treatment, OA management remains challenging, necessitating the development of safe and effective drugs. Quercetin (QUE), a natural flavonoid widely found in fruits and vegetables, shows promise due to its broad range of pharmacological effects, particularly in various degenerative diseases. However, its role in preventing OA progression and its underlying mechanisms remain unclear. In this study, we demonstrated that QUE has a protective effect against OA development both in vivo and in vitro, and we elucidated the underlying molecular mechanisms. In vitro, QUE inhibited the expression of IL-1ß-induced chondrocyte matrix metalloproteinases (MMP3 and MMP13) and inflammatory mediators such as INOS and COX-2. It also promoted the expression of collagen II, thereby preventing the extracellular matrix (ECM). Mechanistically, QUE exerts its protective effect on chondrocytes by activating the SIRT1/Nrf-2/HO-1 and inhibiting chondrocyte ferroptosis. Similarly, in an OA rat model induced by anterior cruciate ligament transection (ACLT), QUE treatment improved articular cartilage damage, reduced joint pain, and normalized abnormal subchondral bone remodeling. QUE also reduced serum IL-1ß, TNF-α, MMP3, CTX-II, and COMP, thereby slowing the progression of OA. QUE exerts chondroprotective effects by inhibiting chondrocyte oxidative damage and ferroptosis through the SIRT1/Nrf-2/HO-1 pathway, effectively alleviating OA progression in rats.

The performance of a Bayesian value-based sequential clinical trial design in the presence of an equivocal cost-effectiveness signal: evidence from the HERO trial.

BACKGROUND: There is increasing interest in the capacity of adaptive designs to improve the efficiency of clinical trials. However, relatively little work has investigated how economic considerations - including the costs of the trial - might inform the design and conduct of adaptive clinical trials. METHODS: We apply a recently published Bayesian model of a value-based sequential clinical trial to data from the 'Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis' (HERO) trial. Using parameters estimated from the trial data, including the cost of running the trial, and using multiple imputation to estimate the accumulating cost-effectiveness signal in the presence of missing data, we assess when the trial would have stopped had the value-based model been used. We used re-sampling methods to compare the design's operating characteristics with those of a conventional fixed length design. RESULTS: In contrast to the findings of the only other published retrospective application of this model, the equivocal nature of the cost-effectiveness signal from the HERO trial means that the design would have stopped the trial close to, or at, its maximum planned sample size, with limited additional value delivered via savings in research expenditure. CONCLUSION: Evidence from the two retrospective applications of this design suggests that, when the cost-effectiveness signal in a clinical trial is unambiguous, the Bayesian value-adaptive design can stop the trial before it reaches its maximum sample size, potentially saving research costs when compared with the alternative fixed sample size design. However, when the cost-effectiveness signal is equivocal, the design is expected to run to, or close to, the maximum sample size and deliver limited savings in research costs.

[Mechanism of Huangqin Qingre Chubi Capsules regulating p53/p21 signaling pathway to delay chondrocyte senescence in osteoarthritic rats].

This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC) in delaying chondrocyte senescence of osteoarthritic(OA) rats by regulating the p53/p21 signaling pathway. Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA) combined with external rheumatic fever environmental stimuli and divided into normal(Con) group, OA model(MIA) group, OA model+rheumatic fever stimulation model(MIA-M) group, MIA-M+HQC low-dose(MIA-M+HQC-L) group, medium-dose(MIA-M+HQC-M) group, and high-dose(MIA-M+HQC-H) group, and MIA-M+glucosamine(MIA-M+GS) group. The models were successfully prepared and administered by gavage for 30 d. The pathological changes of cartilage were observed by hematoxylin-eosin(HE) and Senna O solid green(SO) staining. The expression of interleukin(IL)-1ß and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). Flow cytometry(FCM) was used to detect apoptosis and cell cycle. The mRNA expression of MMP13, ADAMTS-5, COLⅡ, and TGF-ß was detected by RT-qPCR. The protein expression of p53/p21, p16, Bax, and Bcl-2 was detected by Western blot. The articular cartilage surface of rats in the Con group was smooth, and the tide line was smooth. The cartilage layer of MIA and MIA-M groups was obviously damaged, and the cartilage matrix was reduced. The above conditions were more severe in the MIA-M group. The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination. Compared with the MIA-M+HQC-H group, Mankin's score was higher in the HQC low-dose and medium-dose groups, and the change was not obvious in the MIA-M+GS group. Compared with the Con group, the proportion of chondrocytes G_1 was elevated in the MIA and MIA-M groups, and the proportion of the S phase and G_2 phase was significantly decreased. In addition, the apoptosis rate was increased. Compared with MIA-M, HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner. Compared with the MIA-M+HQC-H group, the effect was more significant in the HQC high-dose group than in the HQC medium-low dose, while it was not significant in the MIA-M+GS group. Compared with the Con group, IL-1ß and IL-6 were elevated in the MIA and MIA-M groups, and mRNA levels of MMP13 and ADAMTS-5 were elevated. p53, p21, p16, and Bax protein were elevated, and mRNA levels of COLⅡ and TGF-ß were decreased. Compared with the MIA-M group, IL-1ß and IL-6 decreased after drug interventions of HQC and GS, and mRNA levels of MMP13 and ADAMTS-5, as well as protein levels of p53, p21, Bax, and p16 decreased. In addition, Bcl-2 increased. The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups, and the difference with the MIA-M+GS group was not significant. HQC delayed MIA-induced chondrocyte senescence in OA rats, inhibited inflammatory response and extracellular matrix(ECM) degradation, and its mechanism may be related to the inhibition of the p53/p21 pathway.

The dual amylin and calcitonin receptor agonist KBP-336 elicits a unique combination of weight loss, antinociception and bone protection - a novel disease-modifying osteoarthritis drug.

BACKGROUND: Despite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised (MNX) rats. METHODS: We evaluated KBP-336's effect on pain-like symptoms in Sprague Dawley (SD) rats on high-fat diet (HFD) that underwent meniscectomy using the von Frey test to measure the 50% paw withdrawal threshold (PWT) and analyzed using one-way ANOVA. Short in vivo studies and in vitro cell receptor expression systems were used to illustrate receptor pharmacology. RESULTS: After 30 weeks on HFD, including an 8-week treatment, female MNX animals receiving KBP-336 4.5 nmol/Kg/72 h had lower body weight and smaller adipose tissues than their vehicle-treated counterparts. After 20 weeks on HFD, including an 8-week treatment, male rats receiving KBP-336 had lower body weight than the vehicle group. In both the female and male rats, the MNX groups on KBP-336 treatment had a higher PWT than the vehicle-treated MNX group. Aiming to identify the receptor influencing pain alleviation, KBP-336 was compared to the long-acting human calcitonin (hCTA). Single-dose studies on 12-week-old male rats showed that hCTA lowers CTX-I without affecting food intake, confirming its calcitonin receptor selectivity. On the metabolic OA model with 18 weeks of HFD, including 6-week treatment, hCTA at 100 nmol/Kg/24 h and KBP-336 at 0.5, 1.5, and 4.5 nmol/Kg/72 h produced significantly higher PWT in MNX animals compared to MNX animals on vehicle treatment. hCTA and KBP-336 at 0.5 nmol/Kg did not affect body weight and fat tissues. CONCLUSION: Overall, KBP-336 improved the pain observed in the metabolic OA model. Calcitonin receptor activation proved to be essential in this antinociceptive effect.

Classification of osteoarthritic and healthy cartilage using deep learning with Raman spectra.

Raman spectroscopy is a rapid method for analysing the molecular composition of biological material. However, noise contamination in the spectral data necessitates careful pre-processing prior to analysis. Here we propose an end-to-end Convolutional Neural Network to automatically learn an optimal combination of pre-processing strategies, for the classification of Raman spectra of superficial and deep layers of cartilage harvested from 45 Osteoarthritis and 19 Osteoporosis (Healthy controls) patients. Using 6-fold cross-validation, the Multi-Convolutional Neural Network achieves comparable or improved classification accuracy against the best-performing Convolutional Neural Network applied to either the raw or pre-processed spectra. We utilised Integrated Gradients to identify the contributing features (Raman signatures) in the network decision process, showing they are biologically relevant. Using these features, we compared Artificial Neural Networks, Decision Trees and Support Vector Machines for the feature selection task. Results show that training on fewer than 3 and 300 features, respectively, for the disease classification and layer assignment task provide performance comparable to the best-performing CNN-based network applied to the full dataset. Our approach, incorporating multi-channel input and Integrated Gradients, can potentially facilitate the clinical translation of Raman spectroscopy-based diagnosis without the need for laborious manual pre-processing and feature selection.

Effect of the Sauvé-Kapandji method on the wrist contact surface for distal radial ulnar joint disorders.

BACKGROUND: The Sauvé-Kapandji (S-K) method is a surgical procedure performed for chronic deformities of the distal radial ulnar joint (DRUJ). Changes to the joint contact surface from pre- to postoperatively under physiological in vivo conditions have not yet been determined for this useful treatment. The aim of the present study was therefore to compare the articular contact area of the wrist joint between before and after the S-K method for DRUJ disorders. METHODS: The SK method was performed for 15 patients with DRUJ osteoarthritis and ulnar impaction syndrome. We calculated the Mayo Wrist Score as the patient's clinical findings and created 3-dimensional bone models of cases in which the S-K method was performed and calculated the contact area and shift in the center of the contact area using customized software. RESULTS: The Mean modified Mayo Wrist Score improved significantly from 60.3 preoperatively to 80.3 postoperatively (P < 0.01). Scaphoid contact area to the radius increased significantly from 112.6 ± 37.0 mm2 preoperatively to 127.5 ± 27.8 mm2 postoperatively (P = 0.03). Lunate contact area to radius-ulna was 121.3 ± 43.3 mm2 preoperatively and 112.5 ± 37.6 mm2 postoperatively, but this decrease was not significant (P = 0.38). Contact area ratio of scaphoid to lunate increased significantly from 1.01 ± 0.4 preoperatively to 1.20 ± 0.3 postoperatively (P = 0.02). Postoperative translations of the center of the scaphoid and lunate contact areas were decomposed into ulnar and proximal directions. Ulnar and proximal translation distances of the scaphoid contact area were 0.8 ± 1.7 mm and 0.4 ± 0.6 mm, respectively, and those of the lunate contact area were 1.1 ± 1.7 mm and 0.4 ± 1.1 mm, respectively. This study revealed changes in wrist contact area and center of the contact area before and after the S-K method. CONCLUSION: These results may accurately indicate changes in wrist joint contact area from pre- to postoperatively using the S-K method for patients with DRUJ disorder. Evaluation of changes in contact area due to bone surface modeling of the wrist joint using 3DCT images may be useful in considering surgical methods.

Label-Free and Ultrasensitive Detection of Cartilage Acidic Protein 1 in Osteoarthritis Using a Single-Walled Carbon Nanotube Field-Effect Transistor Biosensor.

Osteoarthritis (OA), a prevalent degenerative joint disease, significantly affects the well-being of afflicted individuals and compromises the standard functionality of human joints. The emerging biomarker, Cartilage acidic protein 1 (CRTAC1), intricately associates with OA initiation and serves as a prognostic indicator for the trajectory toward joint replacement. However, existing diagnostic methods for CRTAC1 are hampered by the limited abundance, thus restricting the precision and specificity. Herein, a novel approach utilizing a single-walled carbon nanotube field-effect transistor (SWCNTs FET) biosensor is reported for the direct label-free detection of CRTAC1. High-purity semiconducting carbon nanotube films, functionalized with antibodies of CRTAC1, provide excellent electrical and sensing properties. The SWCNTs FET biosensor exhibits high sensitivity, notable reproducibility, and a wide linear detection range (1 fg/mL to 100 ng/mL) for CRTAC1 with a theoretical limit of detection (LOD) of 0.2 fg/mL. Moreover, the SWCNTs FET biosensor is capable of directly detecting human serum samples, showing excellent sensing performance in differentiating clinical samples from OA patients and healthy populations. Comparative analysis with traditional enzyme-linked immunosorbent assay (ELISA) reveals that the proposed biosensor demonstrates faster detection speeds, higher sensitivity/accuracy, and lower errors, indicating high potential for the early OA diagnosis. Furthermore, the SWCNTs FET biosensor has good scalability for the combined diagnosis and measurement of multiple disease markers, thereby significantly expanding the application of SWCNTs FETs in biosensing and clinical diagnostics.

Circadian rhythm disruption upregulating Per1 in mandibular condylar chondrocytes mediating temporomandibular joint osteoarthritis via GSK3ß/ß-CATENIN pathway.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) has a high incidence rate, but its pathogenesis remains unclear. Circadian rhythm is an important oscillation in the human body and influences various biological activities. However, it is still unclear whether circadian rhythm affects the onset and development of TMJOA. METHODS: We disrupted the normal rhythm of rats and examined the expression of core clock genes in the mandibular condylar cartilage of the jaw and histological changes in condyles. After isolating rat mandibular condylar chondrocytes, we upregulated or downregulated the clock gene Per1, examined the expression of cartilage matrix-degrading enzymes, tested the activation of the GSK3ß/ß-CATENIN pathway and verified it using agonists and inhibitors. Finally, after downregulating the expression of Per1 in the mandibular condylar cartilage of rats with jet lag, we examined the expression of cartilage matrix-degrading enzymes and histological changes in condyles. RESULTS: Jet lag led to TMJOA-like lesions in the rat mandibular condyles, and the expression of the clock gene Per1 and cartilage matrix-degrading enzymes increased in the condylar cartilage of rats. When Per1 was downregulated or upregulated in mandibular condylar chondrocytes, the GSK3ß/ß-CATENIN pathway was inhibited or activated, and the expression of cartilage matrix-degrading enzymes decreased or increased, which can be rescued by activator and inhibitor of the GSK3ß/ß-CATENIN pathway. Moreover, after down-regulation of Per1 in mandibular condylar cartilage in vivo, significant alleviation of cartilage degradation, cartilage loss, subchondral bone loss induced by jet lag, and inhibition of the GSK3ß/ß-CATENIN signaling pathway were observed. Circadian rhythm disruption can lead to TMJOA. The clock gene Per1 can promote the occurrence of TMJOA by activating the GSK3ß/ß-CATENIN pathway and promoting the expression of cartilage matrix-degrading enzymes. The clock gene Per1 is a target for the prevention and treatment of TMJOA.

MiR-539-3p Alleviates Apoptosis and Extracellular Matrix Degradation in Chondrocytes of Childhood-Onset Osteoarthritis by Targeting RUNX2.

Recent research has identified that miR-539-3p impedes chondrogenic differentiation, yet its specific role and underlying mechanisms in childhood-onset osteoarthritis (OA) remain unclear. This study found that miR-539-3p levels were considerably lower in cartilage samples derived from childhood-onset OA patients compared to the control group. Enhancing miR-539-3p expression or suppressing RUNX2 expression notably reduced apoptosis, inflammation, and extracellular matrix (ECM) degradation in OA chondrocytes. In contrast, reducing miR-539-3p or increasing RUNX2 had the opposite effects. RUNX2 was confirmed as a direct target of miR-539-3p. Further experiments demonstrated that miR-539-3p targeting RUNX2 effectively lessened apoptosis, inflammation, and ECM degradation in OA chondrocytes, accompanied by changes in key molecular markers like reduced caspase-3 and matrix etallopeptidase 13 (MMP-13) levels, and increased B-cell lymphoma 2 (Bcl-2) and collagen type X alpha 1 chain (COL2A1). This study underscores the pivotal role of miR-539-3p in alleviating inflammation and ECM degradation in childhood-onset OA through targeting RUNX2, offering new insights for potential therapeutic strategies against this disease.

Non-coding RNAs as regulators of autophagy in chondrocytes: Mechanisms and implications for osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that do not possess protein-coding functions, but they can act as effective post-transcriptional and epigenetic regulators of gene and protein expression, thus participating in numerous fundamental biological processes. Increasing evidence suggests that ncRNAs, autophagy, and their crosstalk play crucial roles in OA pathogenesis. Therefore, we summarized the complex role of autophagy in OA chondrocytes and focused on the regulatory role of ncRNAs in OA-associated autophagy to elucidate the complex pathological mechanisms of the ncRNA-autophagy network in the development of OA, thus providing new research targets for the clinical diagnosis and treatment of OA.

The dynamic progression of temporomandibular joint osteoarthritis-like lesions elicited by mandibular shift in a rat model.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) presents significant challenges due to its complex etiology, often insidious onset, high incidence, and progressive structural deterioration. While research has explored genetic and molecular factors, treatment outcomes remain suboptimal, emphasizing the need for a deeper understanding of disease progression. OBJECTIVE: This study employs a specific mandibular shift rat model to explore the dynamic progression of TMJ-OA-like lesions and evaluate the potential for self-repair at different stages, aiming to inform early diagnosis and preventative strategies. METHODS: Seventy-two female Sprague-Dawley rats were randomized into three groups: a control group (n=24; average weight: 157.23±1.63 g) receiving sham surgery. an experimental group (n=24; average weight: 157.78±1.88 g) subjected to mandibular shift induction, and a removal group (n=24; average weight: 158.11±2.20 g) experiencing mandibular shift for one, two, or four weeks followed by a one-month recovery period (designated as 1w Removal, 2w Removal and 4w Removal, respectively). Histomorphological and molecular analyses were conducted at designated time points. RESULTS: Rats in the 1-week removal group exhibited substantial recovery in condylar morphology, cartilage thickness, extracellular matrix composition, and expression of OA-related genes. Conversely, the 4-week removal group mirrored the experimental group, indicating limited self-repair capacity at later stages. The 2-week removal group presented with variable outcomes, with some animals showing signs of recovery and others resembling the experimental group, indicating a potential transitional phase in the disease process. CONCLUSION: Recovery from early-stage TMJ-OA involves eliminating provoking factors such as occlusal interference or reducing joint loading. However, advanced stages exhibit diminished self-repair capabilities, necessitating additional therapeutic interventions. These findings emphasize the importance of early diagnosis and intervention in TMJ-OA management.

ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis.

Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize an induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. We show that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Likely owing to the unique features of the collagen triple helix, this accumulation is not recognized by the unfolded protein response. Gly1170Ser procollagen-II interacts to a greater extent than wild-type with specific ER proteostasis network components, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the easily expandable cartilage model will enable rapid testing of therapeutic strategies to restore proteostasis in the collagenopathies.

High revision rate of metal-backed glenoid component and impact on the overall revision rate of stemless total shoulder arthroplasty: a cohort study from the Danish Shoulder Arthroplasty Registry.

BACKGROUND AND PURPOSE: There is controversy regarding the results of stemmed and stemless total shoulder arthroplasty (TSA) used for osteoarthritis. Therefore, we aimed to compare revision rates of stemmed and stemless TSA and to examine the impact of metal-backed glenoid components. METHODS: We included all patients reported to the Danish Shoulder Arthroplasty Register from January 1, 2012 to December 31, 2022 with an anatomical TSA used for osteoarthritis. Primary outcome was revision (removal or exchange of components) for any reason. RESULTS: 3,338 arthroplasties were included. The hazard ratio for revision of stemless TSA adjusted for age and sex was 1.83 (95% confidence interval [CI] 1.21-2.78) with stemmed TSA as reference. When excluding all arthroplasties with a metal-backed glenoid component, the adjusted hazard ratio for revision of stemless TSA was 1.37 (CI 0.85-2.20). For the Eclipse stemless TSA system, the adjusted hazard ratio for revision of a metal-backed glenoid component was 8.75 (CI 2.40-31.9) with stemless Eclipse with an all-polyethylene glenoid component as reference. CONCLUSION:  We showed that the risk of revision of stemless TSAs was increased and that it was related to their combination with metal-backed glenoid components.