Joint Osteoarthritis Research Articles

Relationship between Lumbar Foraminal Stenosis and Multifidus Muscle Atrophy - A Retrospective Cross-Sectional Study.

Retrospective cross-sectional study. To evaluate the relationship between lumbar foraminal stenosis (LFS) and multifidus muscle atrophy. The multifidus muscle is an important stabilizer of the lumbar spine. In LFS, the compression of the segmental nerve can give rise to radicular symptoms and back pain. LFS can impede function and induce atrophy of the segmentally innervated multifidus muscle. Patients with degenerative lumbar spinal conditions who underwent posterior spinal fusion for degenerative lumbar disease from December 2014 to February 2024 were analyzed. Multifidus fatty infiltration (FI) and functional cross-sectional area (fCSA) were determined at the L4 upper endplate axial level on T2- weighted MRI scans using dedicated software. Severity of LFS was assessed at all lumbar levels and sides using the Lee classification (Grade: 0 - 3). For each level, Pfirrmann and Weishaupt gradings were used to assess intervertebral disc disease (IVDD) and facet joint osteoarthritis (FJOA), respectively. Multivariable linear mixed models were run for the LFS grade of each level and side separately as the independent predictor of multifidus FI and fCSA. Each analysis was adjusted for age, sex, BMI, as well as FJOA and IVDD of the level corresponding to the LFS. A total of 216 patients (50.5% female) with a median age of 61.6 years (IQR=52.0 - 69.0) and a median BMI of 28.1kg/m2 (IQR=24.8 - 33.0) were included. Linear mixed model analysis revealed that higher multifidus FI (Estimate [Confidence interval]=1.7% [0.1 - 3.3], P=0.043) and lower fCSA (-18.6mm2 [-34.3 - -2.6], P=0.022) were both significantly predicted by L2-L3 level LFS severity. The observed positive correlation between upper segment LFS and multifidus muscle atrophy points towards compromised innervation. This necessitates further research to establish the causal relationship and guide prevention efforts.

Nonoperative Management of Trapeziometacarpal Joint Arthritis: A Systematic Review of the Clinical Trials.

This systematic review evaluates nonoperative treatments for trapeziometacarpal joint osteoarthritis (TMJO), a common degenerative condition in postmenopausal females causing pain, reduced mobility, and diminished grip strength.Following PRISMA guidelines, a search was conducted across PubMed, Cochrane, Embase, and MEDLINEfor randomized controlled trials (RCTs) assessing pain outcomes with nonoperative interventions over at least a six-month follow-up, using the visual analog scale (VAS) for pain measurement. Eleven RCTs yielded moderate-quality evidence for the following: (1) corticosteroid (CSI) and hyaluronic acid (HA) injections exhibit comparable mean delta pain scores after six months, with CSI offering early relief at two to three weeks. After 12 months, CSI led to a continued decrease in pain, with a mean delta pain score of 1.0 (p<0.05), contrasting with hyaluronic acid (HA) injections, which presented a modest though nonsignificant improvement, demonstrating a mean delta pain score of 0.5 (p=0.16). (2) Relatively novel therapies for TMJO, such as platelet-rich plasma (PRP) and dextrose, appear to surpass CSI in long-term effectiveness, with dextrose showing a mean delta pain score of 3.8 (p<0.001) at six months and PRP achieving a mean delta pain score of 5.5 (p=0.005) at 12 months. (3) Various hand therapies, notably standard hand exercises and extracorporeal shockwave therapy (ESWT), demonstrated significant pain reduction, with the former achieving a mean delta pain score of 1.5 (p=0.019) and the latter a score of 4.2 (p<0.001). (4) The use of orthoses substantially decreases pain levels, demonstrating a mean delta pain score reduction of 2.6 at a 180-day follow-up (p=0.023) and 2.2 at a 12-month follow-up (p=0.002). In conclusion, nonoperative treatments for TMJO, including intra-articular injections, hand therapy, and orthoses, provide significant pain relief at a minimum of six months follow-up. The synergistic effect of combined nonoperative management, as well as the effect size of each, is unknown.

Experiences with Volumetric Modulated Arc Therapy (VMAT) for treating symptomatic peripheral joint osteoarthritis (OA) with Low Dose Radiotherapy (LDRT) – a case series

Introduction: Peripheral joint osteoarthritis (OA) in Australia is the third leading cause of life-years lost. Implant surgery is a great help, but patients who are waiting or are inoperable suffer. Low Dose Radiotherapy (LDRT) is well established in some countries. Three-dimensional conformal radiotherapy (3DCRT) is recommended. However, some departments may only have Volumetric Modulated Arc Therapy (VMAT). We present our experiences treating ten volumes of symptomatic OA treated with VMAT in nine consecutive patients to two months post-LDRT. Methods: The hypothesis was that LDRT using VMAT was feasible and effective at two months. Patient response data was collected prospectively. The Visual Analog Scale Pain (VASP) for pain was used. A Visual Analog Scale Mobility (VASM) was created for mobility. Bones within radiation oncologists (RO) skin marks around the joint were auto-contoured for clinical target volume (CTV) with 2 mm expansion to planning target volume (PTV). Treatment was titrated to clinical response. Phase 1 was 3 Gray (Gy) in 6 fractions at 2-3 fractions per week. There was RO review at 2 months post-phase 1 for consideration of phase 2. If no response, then phase 2 was 6 Gy in 6 fractions, if a partial response (PR), then a repeat of phase 1. A third phase similar to phase 2 was possible. RO follow-up was done 2 months after the last phase. Results: Nine consecutive patients, eight males and one female, average age of 69 years (60-84), with ten volumes of symptomatic OA were treated. Joints were three single knees, two cases of both knees, three cases of both hands, one hip and one carpometacarpal joint. They had suffered from OA for an average of eight years (1-20). All were on at least one systemic therapy. All were using some sort of local therapy or device. Eight had a PR to phase 1 and proceeded to phase 2. Two had an equivocal response. No patient had a third phase. Average VASP pain scores fell from baseline of 7.4 to 3.6 after phase 1, and to 2.3 after phase 2. Average VASM immobility scores fell from baseline of 6.9 to 4.4 after phase 1 and to 3.3 after phase 2. Conclusion: In this small Australian cohort LDRT using VMAT is feasible and clinically effective when measured at 2 months. More study is needed.

17β-estradiol promotes the progression of temporomandibular joint osteoarthritis by regulating the FTO/IGF2BP1/m6A-NLRC5 axis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17β-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms. Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining. The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown. E2 promoted the progression of TMJOA.

Single Injection AAV2-FGF18 Gene Therapy Reduces Cartilage Loss and Subchondral Bone Damage in a Mechanically Induced Model of Osteoarthritis.

Osteoarthritis (OA) is a highly debilitating, degenerative pathology of cartilaginous joints affecting over 500 million people worldwide. The global economic burden of OA is estimated at $260-519 billion and growing, driven by aging global population and increasing rates of obesity. To date, only the multi-injection chondroanabolic treatment regimen of Fibroblast Growth Factor 18 (FGF18) has demonstrated clinically meaningful disease-modifying efficacy in placebo-controlled human trials. Our work focuses on the development of a novel single injection disease-modifying gene therapy, based on FGF18's chondroanabolic activity. OA was induced in Sprague-Dawley rats using destabilization of the medial meniscus (DMM) (3 weeks), followed by intra-articular treatment with 3 dose levels of AAV2-FGF18, rh- FGF18 protein, and PBS. Durability, redosability, and biodistribution were measured by quantifying nLuc reporter bioluminescence. Transcriptomic analysis was performed by RNA-seq on cultured human chondrocytes and rat knee joints. Morphological analysis was performed on knee joints stained with Safranin O/Fast Green and anti-PRG antibody. Dose-dependent reductions in cartilage defect size were observed in the AAV2-FGF18- treated joints relative to the vehicle control. Total defect width was reduced by up to 76% and cartilage thickness in the thinnest zone was increased by up to 106%. Morphologically, the vehicle- treated joints exhibited pronounced degeneration, ranging from severe cartilage erosion and bone void formation, to subchondral bone remodeling and near-complete subchondral bone collapse. In contrast, AAV2-FGF18-treated joints appeared more anatomically normal, with only regional glycosaminoglycan loss and marginal cartilage erosion. While effective at reducing cartilage lesions, treatment with rhFGF18 injections resulted in significant joint swelling (19% increase in diameter), as well as a decrease in PRG4 staining uniformity and intensity. In contrast to early-timepoint in vitro RNA-seq analysis, which showed a high degree of concordance between protein- and gene therapy-treated chondrocytes, in vivo transcriptomic analysis, revealed few gene expression changes following protein treatment. On the other hand, the gene therapy treatment exhibited a high degree of durability and localization over the study period, upregulating several chondroanabolic genes while downregulating OA- and fibrocartilage-associated markers. FGF18 gene therapy treatment of OA joints can provide benefits to both cartilage and subchondral bone, with a high degree of localization and durability.

The Effect of Intra-Articular Injections of Hyaluronic Acid for the Treatment of Trapezio-Metacarpal Joint Osteoarthritis.

Osteoarthritis of the basal thumb joint is a debilitating disease with a high prevalence. Among pharmacological treatments, intra-articular injections of hyaluronic acid have been clinically applied. This study aimed to investigate the effectiveness and safety of intra-articular injections of hyaluronic acid for the treatment of trapezio-metacarpal joint osteoarthritis (TMOA), over a one-year period. Patients with TMOA were enrolled and treated with five consecutive intra-articular injections of hyaluronic acid (20 mg/2 mL, 500-750 KDa, HyalganBio) at weekly intervals. Primary outcomes were pain during different activities (changes in numerical rating scale) and function (pinch and grip strength), and secondary outcomes were safety (adverse events) and patient-reported outcomes (quick-DASH and SF-12). The outcomes were evaluated at baseline and 1-, 3-, 6-, and 12- months after the last injection. A total of 29 patients were included. All participants completed the five injective sessions and the first follow-up. A total of 15 patients completed the study. During the follow-up period, intra-articular injections of hyaluronic acid have significantly reduced spontaneous and provoked pain and improved disability. No severe systemic adverse events were reported. At a follow-up of up to 12 months, patients with TMOA treated with intra-articular hyaluronic acid injections reported improvements in pain relief and quality of life.

Can temporomandibular joint osteoarthritis be diagnosed on MRI proton density weighted images with diagnostic support from the latest deep learning classification models?

This study aimed to clarify the performance of magnetic resonance imaging (MRI)-based deep learning classification models in diagnosing temporomandibular joint osteoarthritis (TMJ-OA) and to compare the developed diagnostic assistance with human observers. The subjects were 118 patients who underwent MRI for examination of TMJ disorders. One hundred condyles with TMJ-OA and 100 condyles without TMJ-OA were enrolled. Deep learning was performed with four networks (ResNet18, EfficientNet b4, Inception v3, and GoogLeNet) using five-fold cross validation. Receiver operating characteristics (ROC) curves were drawn for each model and diagnostic metrics were determined. The performances of the four network models were compared using Kruskal-Wallis tests and post-hoc Scheffe tests, and ROCs between the best model and human were compared using chi-square tests, with p < 0.05 considered significant. ResNet18 had areas under the curves (AUCs) of 0.91-0.93 and accuracy of 0.85-0.88, which were the highest among the four networks. There were significant differences in AUC and accuracy between ResNet and GoogLeNet (p = 0.0264 and p = 0.0418, respectively). The kappa values of the models were large, 0.95 for ResNet and 0.93 for EfficientNet. The experts achieved similar AUC and accuracy values ​​to the ResNet metrics, 0.94 and 0.85, and 0.84 and 0.84, respectively, but with a lower kappa of 0.67. Those of the dental residents showed lower values. There were significant differences in AUCs between ResNet and residents (p < 0.0001) and between experts and residents (p < 0.0001). Using a deep learning model, high performance was confirmed for MRI diagnosis of TMJ-OA.

A prospective, randomised, controlled, double blinded, cross-over study on the effect of a single session of pulsed electromagnetic field therapy on signs of hip osteoarthritis in dogs

BackgroundCanine coxofemoral joint osteoarthritis is a common, painful and debilitating condition. The objective of this study was to evaluate if any measurable changes in pain or lameness occurred in this patient group immediately after a single treatment with pulsed electromagnetic field therapy. Eight dogs with coxofemoral joint osteoarthritis presenting with signs of pain and lameness were prospectively recruited to this randomised, controlled, double blinded, cross-over study. Subjects attended the research facility on two occasions for one active and one placebo treatment with pulsed electromagnetic field therapy. The immediate effect of one pulsed electromagnetic field therapy treatment on pain and lameness was measured subjectively with the Helsinki Chronic Pain Index and Visual Analogue Scale and objectively using a pressure sensitive walkway.ResultsA statistically significant difference (P = 0.03) for change in stride length in the affected limb was recorded for subjects between the active and placebo treatments with pulsed electromagnetic field therapy. Within the active treatment results, there was a statistically significant change in the measurement for reach (P = 0.04) and stride length (P = 0.047) which got shorter in the affected limb post treatment. For the subjective outcome measures, there was no statistically significant difference between the active and placebo treatments for the evening of the treatment day or the next morning from pre-treatment values. Within the placebo treatment results a statistically significant change (improvement) was detected in Visual Analogue Score (P = 0.03) between pre-treatment and the next morning values.ConclusionsThe findings of this study do not show demonstrable improvement in owner assessed pain levels or temporospatial performance in dogs with coxofemoral joint osteoarthritis immediately after a single application of pulsed electromagnetic field therapy.

An Application of the Scaled–Pixel–Counting Protocol to Quantify the Radiological Features of Anatomical Structures of the Normal Tarsal Joint in Horses

Abstract Background: As high-performance human and equine athletes train and compete at the highest level of effort, the prevention of high-performance-cased diseases, such as osteoarthritis (OA), requires knowledge of the anatomy and physiology of the subjected bones. Objective: Implementation of the scaled–pixel–counting protocol to quantify the radiological features of anatomical structures of the normal equine tarsal joint as the first step in the prevention of the tarsal joints OA in high-performance sport horses. Methods: A radiographic examination was performed in six cadaverous equine pelvic limbs. The dorso–plantar projection of the tarsal joint was performed using density standard (DS) attached to the radiographic cassette, standard X-ray equipment and standard diagnostic imaging protocol. On each of the radiographs, pixel brightness (PB) was extracted for each of the 10 steps (S1–S10) of DS. On each of the radiographs, seven regions of interest (ROIs) were annotated representing four bones (II tarsal bone [II TB], III tarsal bone [III TB], IV tarsal bone [IV TB] and central tarsal bone [CTB]) and three joints (proximal intertarsal joint [PIJ], distal intertarsal joint [DIJ] and tarsometatarsal joint [TMJ]), respectively. For each ROI, the percentage (%) of number of pixels (NP) from each range was calculated. Results: The % of NP was lower in bones than in joint spaces for S1–S6 and was higher in bones than in joint spaces for S8–S10. The % of NP was higher in PIJ than TMJ for S1 and higher in PIJ than DIJ for S4. No differences were found between consecutive bones for all examined steps of DS. Conclusions: An application of the scaled–pixel–counting protocol provides the quantitative radiological features of normal bone and joint structures of the tarsal joint in horses, making possible differentiation of the lucency of joint space and opacity of bone structure.

Comparative evaluation of knee osteoarthritis: radiography vs. ultrasonography in Nepalese population: a cross-sectional study.

Osteoarthritis (OA) is a degenerative and long-term debilitating disease with rising prevalence, predominantly involving larger joints including the knee joint. While radiography has traditionally been the primary modality for joint evaluation, there is a growing trend towards using ultrasonography (USG) for musculoskeletal disorders, including joint assessment. This study aimed to find the role of USG in the evaluation of OA of knee joints with comparison to the radiographs. This was a cross-sectional study done on patients with signs and symptoms of OA of the knee who visited the radiology department for knee radiographs. Kellgren and Lawrence system was used for grading OA in radiographs. USG of knee joints was done with high-frequency probes and searched for joint space width, articular cartilage thickness, marginal osteophytes, meniscal extrusion, and other articular/ extra-articular abnormalities. The USG findings were correlated with findings in anteroposterior and lateral radiographs. The mean number of osteophytes was higher in USG compared to the radiographs (P<0.001). Mean joint spaces were comparable in both modalities. Meniscal extrusion was seen with USG, which significantly correlated with joint space width and cartilage thickness (P<0.005). USG also detected synovial changes, effusion, and Baker's cyst. Although radiography is the standard first-line radiological investigation for the diagnosis of OA of the knee joint, USG can be an adjunct as it well correlates with the radiograph findings and can provide more useful information.

Development of an Ultrasound Imaging Atlas for Grading Osteoarthritis in the First Metatarsophalangeal Joint.

Ultrasound (US) imaging may play a fundamental role in the earlier detection and assessment of first metatarsophalangeal joint (MTPJ) osteoarthritis (OA) because of its ability to depict tissue-specific morphologic changes before the point of irreversible structural damage. However, the role of US in supporting the diagnosis of OA in foot joints has not been clearly defined. The aims of this study were to develop a semiquantitative US atlas (the AUT ultrasound imaging [AUTUSI] atlas) to grade the degree of osteoarthritic change in the first MTPJ and to evaluate the intraexaminer and interexaminer reproducibility of using the atlas. US images were obtained from 57 participants (30 participants with radiographically confirmed first MTPJ OA). The AUTUSI atlas supports the examination of grading joint effusion, synovial hypertrophy, synovitis, osteophytes, joint space narrowing, and cartilage thickness. Six examiners used the atlas to independently grade 24 US images across 2 sessions. Intraexaminer and interexaminer reproducibility were determined using percentage agreement and Gwet's AC2. Observations using the AUTUSI atlas demonstrated almost perfect-to-perfect interexaminer agreement (percentage agreement ranged from 96% to 100%, and Gwet's AC2 values ranged from 0.81 to 1.00) and moderate-to-perfect intraexaminer agreement (percentage agreement ranged from 67% to 100%, and Gwet's AC2 values ranged from 0.54 to 1.00). The AUTUSI atlas demonstrated excellent intraexaminer and interexaminer reproducibility for evaluating first MTPJ joint effusion, synovial hypertrophy, synovitis, joint space narrowing, osteophytes, and cartilage thickness. The AUTUSI atlas affords an opportunity to detect prognostic markers of OA earlier in the disease cascade and has the potential to advance understanding of the pathologic process of first MTPJ OA.

An Advanced Case of TMJ Osteoarthritis

Advanced temporomandibular joint (TMJ) osteoarthritis can present with several complications, including synovial cyst formation. Through this work , we present a case of a 69-year-old patient with bilateral painful swelling in the parotid regions, he previously operated for goiter in 2003 without any complications. Magnetic resonance imaging (MRI) revealed bilateral temporomandibular joint effusion with a cystic formation on the left, extending from the posterior border of the masseter muscle to the anterior margin of the superficial lobe of the parotid gland, communicating with the joint space. Additionally, there were findings of TMJ irregularities, condylar degeneration, and contrast-enhancing synovial thickening indicative of osteoarthritis. Computed tomography (CT) complement highlighted bilateral condylar flattening with joint space narrowing and osteoarthritic changes

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

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. 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. 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. 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. Trapeziectomy with WALANT for TMJ OA is safe, preferred by patients and has similar clinical outcome as trapeziectomy in general anesthesia. trapeziectomy, osteoarthritis, WALANT.

Therapeutic Effects of PEG-Modified Polyamide Amine Dendrimer for Cell Free DNA Adsorption in Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJ OA) is characterized by the degeneration of cartilage and subchondral bone. In this study, we observed a significant increase in cell-free DNA (cfDNA) levels during the progression of TMJ OA. Bioinformatics analysis identified TLR9 as a pivotal molecule in TMJ OA pathogenesis. The polyamidoamine (PAMAM) dendrimer characterized by a well-structured, highly branched, and reactive nature, exhibits robust binding and clearance capabilities for cfDNA. However, the abundant amino groups on the surface of PAMAM lead to its inherent toxicity. To mitigate this, PEG-5000 was conjugated to the surface of PAMAM dendrimers, enhancing safety. Our results indicate that PEG-PAMAM effectively inhibits the upregulation of the TLR9 protein in TMJ OA, significantly suppressing the activation of the p-IκBα/p-NF-κB signaling pathway and subsequently decreasing chondrocyte inflammation and apoptosis, as evidenced by both in vivo and in vitro experiments. We conclude that PEG-PAMAM is a safe and effective material for in vivo applications, offering a promising therapeutic strategy for TMJ OA by targeting cfDNA clearance.

Integrin signalling in joint development, homeostasis and osteoarthritis.

Integrins are key regulators of cell-matrix interactions during joint developmentand joint tissue homeostasis, as well as inthe development of osteoarthritis (OA). The signalling cascades initiated by the interactions of integrins with a complex network of extracellular matrix (ECM) components and intracellular adaptor proteins orchestrate cellular responses necessary for maintaining joint tissue integrity. Dysregulated integrin signalling, triggered by matrix degradation products such as matrikines, disrupts this delicate balance, tipping the scales towards an environment conducive to OA pathogenesis. The interplay between integrin signalling and growth factor pathways further underscores the multifaceted nature of OA. Moreover, emerging insights into the role of endocytic trafficking in regulating integrin signalling add a new layer of complexity to the understanding of OA development. To harness the therapeutic potential of targeting integrins for mitigation of OA, comprehensive understanding of their molecular mechanisms across joint tissues is imperative. Ultimately, deciphering the complexities of integrin signalling will advance the ability to treat OA and alleviate its global burden.

Circadian rhythm disruption upregulating Per1 in mandibular condylar chondrocytes mediating temporomandibular joint osteoarthritis via GSK3β/β-CATENIN pathway

BackgroundTemporomandibular 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.MethodsWe 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 GSK3β/β-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.ResultsJet 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 GSK3β/β-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 GSK3β/β-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 GSK3β/β-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 GSK3β/β-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.

Intra-articular sprouting of nociceptors accompanies progressive osteoarthritis: comparative evidence in four murine models.

Knee joints are densely innervated by nociceptors. In human knees and rodent models, sprouting of nociceptors has been reported in late-stage osteoarthritis (OA). Here, we sought to describe progressive nociceptor remodeling in early and late-stage OA, using four distinct experimental mouse models. Sham surgery, destabilization of the medial meniscus (DMM), partial meniscectomy (PMX), or non-invasive anterior cruciate ligament rupture (ACLR) was performed in the right knee of 10-12-week old male C57BL/6 NaV1.8-tdTomato mice. Mice were euthanized (1) 4, 8 or 16 weeks after DMM or sham surgery; (2) 4 or 12 weeks after PMX or sham; (3) 1 or 4 weeks after ACLR injury or sham. Additionally, a cohort of naïve male wildtype mice was evaluated at age 6 and 24 months. Mid-joint cryosections were assessed qualitatively and quantitatively for NaV1.8+ or PGP9.5+ innervation. Cartilage damage, synovitis, and osteophytes were assessed. Progressive OA developed in the medial compartment after DMM, PMX, and ACLR. Synovitis and associated neo-innervation of the synovium by nociceptors peaked in early-stage OA. In the subchondral bone, channels containing sprouting nociceptors appeared early, and progressed with worsening joint damage. Two-year old mice developed primary OA in the medial and the lateral compartment, accompanied by nociceptor sprouting in the synovium and the subchondral bone. All four models showed increased nerve signal in osteophytes. These findings suggest that anatomical neuroplasticity of nociceptors is intrinsic to OA pathology. The detailed description of innervation of the OA joint and its relationship to joint damage might help in understanding OA pain.

Effect of Apitoxin versus Hyaluronic Acid in Treatment of Induced Temporomandibular Joint Osteoarthritis in Albino Rats: An Experimental Study.

Effect of Apitoxin versus Hyaluronic Acid in Treatment of Induced Temporomandibular Joint Osteoarthritis in Albino Rats: An Experimental Study.

Alpha-ketoglutarate ameliorates age-related and surgery induced temporomandibular joint osteoarthritis via regulating IKK/NF-κB signaling.

Recent studies have shed light on the important role of aging in the pathogenesis of joint degenerative diseases and the anti-aging effect of alpha-ketoglutarate (αKG). However, whether αKG has any effect on temporomandibular joint osteoarthritis (TMJOA) is unknown. Here, we demonstrate that αKG administration improves condylar cartilage health of middle-aged/aged mice, and ameliorates pathological changes in a rat model of partial discectomy (PDE) induced TMJOA. Invitro, αKG reverses IL-1β-induced/H2O2-induced decrease of chondrogenic markers (Col2, Acan and Sox9), and inhibited IL-1β-induced/ H2O2-induced elevation of cartilage catabolic markers (ADAMTS5 and MMP13) in condylar chondrocytes. In addition, αKG downregulates senescence-associated (SA) hallmarks of aged chondrocytes, including the mRNA/protein level of SA genes (p16 and p53), markers of nuclear disorders (Lamin A/C) and SA-β-gal activities. Mechanically, αKG decreases the expressions of p-IKK and p-NF-κB, protecting TMJ from inflammation and senescence-related damage by regulating the NF-κB signaling. Collectively, our findings illuminate that αKG can ameliorate age-related TMJOA and PDE-induced TMJOA, maintain the homeostasis of cartilage matrix, and exert anti-aging effects in chondrocytes, with a promising therapeutic potential in TMJOA, especially age-related TMJOA.

Bushen Huoxue decotion-containing serum prevents chondrocyte pyroptosis in a m6A-dependent manner in facet joint osteoarthritis

BackgroundFacet joint osteoarthritis (FJOA) is a common lumbar osteoarthritis characterized by degeneration of small joint cartilage. Bushen Huoxue decotion (BSHXD) has good therapeutic effects on OA. Our work aimed to further probe the pharmacological effects of BSHXD-containing serum (BSHXD-CS) on FJOA and define underlying the mechanisms invovled. MethodsTo establish a FJOA cell model, primary rat chondrocytes were treated with LPS. The mRNA and protein expressions were assessed using qRT-PCR and western blot, respectively. The secretion levels of pro-inflammatory cytokines were measured by ELISA. Cell viability was determined by CCK8 assay. The global m6A level was detected by the kit, and NLRP3 mRNA m6A level was determined by Me-RIP assay. The molecular interactions were analyzed by RIP and RNA pull-down assays. ResultsBSHXD-CS treatment relieved LPS-induced cell injury, inflammation, NLRP3 inflammasome and pyroptosis in chondrocytes (all p < 0.05). LPS-induced NLRP3 upregulation in chondrocytes was related to its high m6A modification level (p < 0.05). It was also observed that BSHXD-CS reduced LPS-induced m6A modification in chondrocytes via repressing STAT3 (all p < 0.05), suggesting BSHXD-CS could repress NLRP3 expression via m6A-dependent manner. Moreover, DAA, a m6A specific inhibitor, was proved to strengthen the protectively roles of BSHXD-CS on LPS-challenged pytoptosis (all p < 0.05). ConclusionBSHXD-CS inhibited NLRP3 inflammasome activation and pyroptosis in chondrocytes to repress OA progression by reducing RNA m6A modification.