Articular Damage Research Articles

Knee osteoarthritis: Current status and research progress in treatment (Review).

Knee osteoarthritis (KOA) is a common chronic articular disease worldwide. It is also the most common form of OA and is characterized by high morbidity and disability rates. With the gradual increase in life expectancy and ageing population, KOA not only affects the quality of life of patients, but also poses a burden on global public health. OA is a disease of unknown etiology and complex pathogenesis. It commonly affects joints subjected to greater loads and higher levels of activity. The knee joint, which is the most complex joint of the human body and bears the greatest load among all joints, is therefore most susceptible to development of OA. KOA lesions may involve articular cartilage, synovium, joint capsule and periarticular muscles, causing irreversible articular damage. Factors such as mechanical overload, inflammation, metabolism, hormonal changes and ageing serve key roles in the acceleration of KOA progression. The clinical diagnosis of KOA is primarily based on combined analysis of symptoms, signs, imaging and laboratory examination results. At present, there is no cure for KOA and the currently available therapies primarily focus on symptomatic treatment and delay of disease progression. Knee replacement surgery is typically performed in patients with advanced disease. The current study presents a review of epidemiological characteristics, risk factors, histopathological manifestations, pathogenesis, diagnosis, treatment modalities and progress in KOA research.

Development and in vivo evaluation of therapeutic phytosomes for alleviation of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with progressive articular damage, functional loss and comorbidity. Conventional RA therapy requires frequent dosing and prolonged use, and usually results in poor efficacy and severe toxicity. In the current study, for the first time, we describe a combination strategy using phytosomes co-loaded with curcumin (CUR) and leflunomide (LEF) to improve the clinical outcomes of RA therapy. Exploiting 23 factorial design, various compositions of CUR and LEF co-loaded phytosomes (CUR/LEF-phytosomes) were successfully prepared and were extensively characterized (e.g., particle size, zeta potential, drugs encapsulation efficiency, morphology, DSC, FTIR and release kinetics). The optimal CUR/LEF-loaded phytosomes (F2) demonstrated high stability and spherical morphology with a particle size of ca. 760 nm and negative zeta potential value of − 55.7, high entrapment for both drugs, and sustained release profile of the entrapped medications. In vivo, oral administration of the CUR/LEF-phytosomes (F2) in arthritic rats resulted in significant reduction of paw swelling and inflammatory markers, compared to the free drugs and their physical mixture. Histopathological examination revealed significant improvement in phytosomes-treated animal group with no signs of arthritis. CUR/LEF-loaded phytosomes provide an auspicious strategy for alleviation of RA.

Identification of immunological characteristics and cuproptosis-related molecular clusters in Rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterised by progressive articular damage, functional loss, and comorbidities. The relationship between cuproptosis, a form of programmed cell death, and RA remains unknown. Therefore, this study aimed to explore cuproptosis-related molecular clusters in RA. MethodsGene expression profiles of GSE93272 were downloaded from the Gene Expression Omnibus to identify the expression profiles of cuproptosis regulators and the immune infiltration characteristics of RA. The molecular clusters of cuproptosis-related genes and the related immune cell infiltration were explored. Cluster-specific differentially expressed genes were identified using the weighted gene co-expression network analysis. Further, an external dataset (GSE15573) was used, and an enzyme-linked immunosorbent assay was performed to validate the predictive efficiency. ResultsThirteen cuproptosis-related genes and activated immune responses were identified between patients with RA and controls. Immune infiltration revealed significant immunological heterogeneity in the two cuproptosis-related molecular clusters in RA. Functional enrichment indicated that Cluster1 and Cluster2 were predominantly enriched in the toll-like receptor signalling pathway and regulation of autophagy, respectively. Further, the performance of FAM96A and CGRRF1 genes in the external validation dataset was observed to be relatively satisfactory (area under the receiver operating characteristic curve = 0.687 and 0.674, respectively). Based on our serum samples, FAM96A and CGRRF1 both exhibited higher expression levels in patients with RA (p = 0.001; p = 0.000). ConclusionsOur study systematically illustrated the involvement of cuproptosis in the progression of RA, and explored the pathogenic mechanisms and novel therapeutic strategies for RA, targeting FAM96A and CGRRF1.

Simulated Weightbearing and Articular Injury From Transarticular Screws in a Ligamentous Lisfranc Injury Model.

Transarticular screw fixation is a common surgical treatment for tarsometatarsal ligamentous (Lisfranc) injuries. Iatrogenic damage to articular cartilage from screw placement, however, has been thought to potentially lead to increased risk of tarsometatarsal (TMT) joint arthritis after initial injury. To date, no study has evaluated the effect of weightbearing on articular cartilage after screw fixation. The aim of this study was to create a Lisfranc injury and quantify and compare articular damage due to screw fixation before and after simulated weightbearing. A ligamentous Lisfranc injury was created in 10 cadaveric specimens and treated with transarticular screws. Specimens were cycled for 1000 cycles at 250 N to simulate 2 weeks of physiologic weightbearing. Rotation and diastasis across the Lisfranc complex were measured. Articular injury as a percentage of total articular surface was measured using digital imaging of the first and second TMT joint before and after simulated weightbearing. Comparisons between articular damage were made and statistical analysis was performed. Simulated partial weightbearing increased articular injury 1.44-fold (P < .001). The second metatarsal (M2) showed the greatest increase (1.54-fold, P = .0047), whereas the first (M1) showed the least (1.35-fold, P = .0083). Increases seen at the medial (1.43-fold, P = .0387) and middle cuneiform (1.44-fold, P = .0292) were intermediate between the values seen at M2 and M1. Articular damage from transarticular screw fixation significantly increased after simulated partial weightbearing. This may increase the risk of arthritis and future morbidity when using transarticular screws for the treatment of ligamentous Lisfranc injuries. Iatrogenic damage to articular cartilage due to screw fixation of ligamentous Lisfranc injuries may be increased with weightbearing.

Handgrip strength, physical activity, and body composition in young adults with juvenile idiopathic arthritis

Background. Handgrip strength (HGS) and physical activity (PA) reflect an individual’s overall health and can predict morbidity and mortality. The purpose of the study was to investigate the level of PA and HGS and associated factors in young adults with juvenile idiopathic arthritis (JIA) and determine the connection with body composition parameters. Materials and methods. We conducted a cross-sectional monocentric study of 40 young adults aged 18–30. We collected data on PA and anthropometric and clinical measurements, including disease activity and articular and extra-articular damages. All patients had the following evaluations performed: body composition (dual X-ray absorptiometry), PA level (International Physical Activity Questionnaire), and HGS measurement (using manual hand dynamometer). Results. Sixteen (40 %) patients were considered sedentary, and 32 (80 %) JIA patients had low HGS. The reduced HGS was likely in women, patients with lower body mass index, higher disease activity, and articular damage. In contrast, bone mineral density (BMD) and lean mass were protective factors for reduced HGS (p &lt; 0.05). The level of PA was positively correlated with BMD and lean mass and negatively correlated with fat mass, swollen joint count, and articular damage (p &lt; 0.05). Conclusions. JIA leads to changes in body composition parameters, particularly lean (muscle) mass and muscle strength, and therefore is a risk factor for the development of sarcopenia.

Disability and disease-related damage in Thai children and adolescents with juvenile idiopathic arthritis

BackgroundChildren and adolescents with juvenile idiopathic arthritis (JIA) may suffer from disability and disease-related damage. This study aimed to investigate the prevalence of disability and damage, and identify the factors associated with articular and extra-articular damage in children and adolescents with JIA in a resource-restricted setting in Thailand.MethodsThis cross-sectional study enrolled JIA patients during June 2019-June 2021. Disability was assessed using the Child Health Assessment Questionnaire (CHAQ) and Steinbrocker classification criteria. Damage was evaluated using the Juvenile Arthritis Damage Index (JADI) and the modified-JADI (mJADI) tools.ResultsThere were 101 patients (50.5% female) with median age of 11.8 years. Median disease duration was 32.7 months. Enthesitis-related arthritis (ERA) was the most common subtype (33.7%), followed by systemic JIA (25.7%). Thirty-three (32.7%) patients had delayed diagnosis ≥ 6 months. Moderate to severe disability was found in 20 (19.8%) patients. Patients with Steinbrocker functional classification > class I were seen in 17.9%. Thirty-seven (36.6%) patients had articular damage. Extra-articular complications were observed in 24.8%. Growth failure and striae were the most common complications in 7.8%. Leg-length discrepancy was documented in 5.0%. Ocular damage was found in 1 patient with ERA. Multivariable logistic regression analysis revealed Steinbrocker functional classification > class I (aOR: 18.1, 95% CI: 3.9–84.6; p < 0.001), delayed diagnosis ≥ 6 months (aOR: 8.5, 95%CI: 2.7–27.0; p < 0.001), and ERA (aOR: 5.7, 95%CI: 1.8–18.3; p = 0.004) as independent predictors of articular damage. Systemic corticosteroids use was the independent predictor of extra-articular damage (aOR: 3.8, 95%CI: 1.3–11.1; p = 0.013).ConclusionsDisability and disease-related damage was identified in one-fifth and one-third of JIA patients. Early detection and treatment are essential for preventing permanent damage.

Poster 325: Untreated Ruptures of the Anterior Cruciate Ligament: a 54 Year Follow-Up Study

Poster 325: Untreated Ruptures of the Anterior Cruciate Ligament: a 54 Year Follow-Up Study

Effects of Mongolian Medicine Sengdeng-4 in Rabbit Knee Osteoarthritis Model

Objectives: Seng ldeng-4(SD-4) has a long history of use in Mongolian medical clinics for the treatment for rheumatic disorders. The objective of this study was to investigate the therapeutic effect and mechanism of SD-4 on rabbits with knee osteoarthritis induced by Hulth’s method.Methods: SD-4 (0.428and 0.857g·kg-1) or Zhuangguguanjie pill (0.514g·kg-1) were orally administered in rabbits for four weeks after the induction of knee osteoarthritis using Hulth’s method. Inflammation factors (TNF-α, IL-1β, and NO) and histopathological lesions in the knee joint were examined by ELISA and HE is staining. The expression of type II collagen mRNA in the articular cartilage was detected using real-time qPCR.Results: SD-4 ameliorated the articular lesion damage caused by Hulth’s method in rabbits and reduced the serum levels of inflammatory cytokines TNF-α, IL-1β, and NO. The qPCR results showed that the mRNA expression of type II collagen (COL2) and miRNA-140 gene in the model group was significantly lower than that in the control group (P&lt;0.01), while SD-4 treatment significantly elevated their expressions in the articular cartilage.Conclusion: SD-4 can improve articular cartilage morphology and inflammation by regulating miRNA-140 and COL2 gene expressions, and thus ameliorating knee osteoarthritis of rabbits induced by Hulth’s method.

Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms

BackgroundChildren with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene polymorphisms and serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB-ligand (RANKL) and RANKL/OPG ratio on BMD in children with JIA.MethodsOPG gene rs2073617, rs3134069, serum RANKL, OPG and RANKL/OPG ratio were evaluated in 60 JIA children and 100 matched healthy controls. BMD was evaluated by lumbar dual energy X-ray absorptiometry (DEXA) according to which patients were classified in 2 groups (DEXA z-score above and below − 2). Composite disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS) 27-joints. Articular damage was scored using the juvenile arthritis damage index (JADI).ResultsPatients aged 12.05 ± 3.2 years, included 38 females and 31% had BMD z-score below-2. Systemic-onset JIA was the most frequent phenotype (38%). Genotypes and alleles frequencies of the 2 studied polymorphisms did not differ between patients and controls (p > 0.05 for all) while serum RANKL and RANKL/OPG ratio were significantly higher in patients compared to controls (p = < 0.001 and 0.03 respectively). Patients with BMD < -2 had significantly greater frequencies of rs2073617 TT genotype and T allele (p < 0.001), higher serum RANKL, RANKL/OPG ratio (p = 0.01, 0.002), female predominance (p = 0.02), higher articular and extra-articular damage index (p = 0.008,0.009) and more frequent steroid usage (p = 0.02) compared to patients with BMD z-score >-2. Multivariate analysis showed rs2073617 TT genotype, RANKL/OPG ratio, long disease duration (above 36 months) and use of steroid to be associated with decreased BMD (p = 0.03,0.04,0.01,0.01 respectively) in JIA children.ConclusionsEgyptian children with JIA have decreased BMD. rs2073617 TT genotype and T allele, RANKL/OPG ratio are possible determinants of reduced BMD in JIA. Our results underline the importance of frequent monitoring of BMD in JIA children and trying to control disease activity to preserve long term bone health.

Endothelial Stat3 activation promotes osteoarthritis development.

The mechanism of the balance between subchondral angiogenesis and articular damage within osteoarthritis (OA) progression remains a mystery. However, the lack of specific drugs leads to limited clinical treatment options for OA, frequently failing to prevent eventual joint destruction in patients. Increasing evidence suggests that subchondral bone angiogenesis precedes cartilage injury, while proliferating endothelial cells (ECs) induce abnormal bone formation. Signal transducer and activator of transcription 3 (Stat3) is triggered by multiple cytokines in the OA microenvironment. Here, we observed elevated Stat3 activation in subchondral bone H-type vessels. Endothelial Stat3 activation will lead to stronger cell proliferation, migration and angiogenesis by simulating ECs in OA. In contrast, either Stat3 activation inhibition or knockdown of Stat3 expression could relieve such alterations. More interestingly, blocking Stat3 in ECs alleviated angiogenesis-mediated osteogenic differentiation and chondrocyte lesions. Stat3 inhibitor reversed surgically induced subchondral bone H-type vessel hyperplasia in vivo, significantly downregulating vessel volume and vessel number. Due to the reduced angiogenesis, subchondral bone deterioration and cartilage loss were alleviated. Overall, our data suggest that endothelial Stat3 activation is an essential trigger for OA development. Therefore, targeted Stat3 blockade is a novel promising therapeutic regimen for OA.

Los Polimorfismos en la Uteroglobina y en IL2R están asociados con el daño articular y/o la Cirugía articular en pacientes con Artritis Reumatoide

Introduction and Objectives. Of all clinical manifestations that mark prognosis of a patient with RA, radiological damaged is considered one of the most important variables. In addition to clinical and laboratory markers are increasingly studying the influence of genetic factors in the predictive ability of the RA forecast. Previous studies have reported misleading results about polymorphisms in different genes associated with radiological damage in RA. The aim of this study was to assess the involvement of the clinical, analytical and genetic variables in the radiological damage in a Spanish RA population. Methods. Six hundred thirty-two Spanish RA patients were included. SNP genotyping was performed using an oligonucleotide microarray. Allele and genotype association analyses with articular damage and a haplotype association test were performed. Results. This study includes retrospectively 604 Spanish RA patients with articular erosions and 616 with surgery due to RA. The A587G polymorphism (rs3741240) in uteroglobin gene was associated with increased radiological damage defined by phenotypes RX2 (multiple erosions on hands and feet) and surgery due to RA (OR 1.6 and 1.7 respectively). IL2R polymorphism was associated with RX2 phenotype (OR 2.95). Disease duration, painful joints, ESR, RF and ACPA are the analytical and clinical variables significantly associated with articular damage. Conclusions. These results demonstrate that the A587G and C4599T polymorphism in uteroglobin and IL2R genes respectively are associated with radiological damage in a Spanish RA population.

Nanomedicine is more than a supporting role in rheumatoid arthritis therapy.

Rheumatoid arthritis(RA) is an autoimmune disorder that affects the joints. Various medications successfully alleviate the symptoms of RA in clinical. Still, few therapy strategies can cure RA, especially when joint destruction begins, and there is currently no effective bone-protective treatment to reverse the articular damage. Furthermore, the RA medications now used in clinical practice accompany various adverse side effects. Nanotechnology can improve the pharmacokinetics of traditional anti-RA drugs and therapeutic precision through targeting modification. Although the clinical application of nanomedicines for RA is in its infancy, preclinical research is rising. Current anti-RA nano-drug studies mainly focus on the following: drug delivery systems, nanomedicines with anti-inflammatory and anti-arthritic properties, biomimetic design with better biocompatibility and therapeutic features, and nanoparticle-dominated energy conversion therapies. These therapies have shown promising therapeutic benefits in animal models, indicating that nanomedicines are a potential solution to the current bottleneck in RA treatment. This review will summarize the present state of anti-RA nano-drug research.

The Role of TNF-α in Rheumatoid Arthritis

Rheumatoid arthritis (RA) induces articular damage through autoimmunity. Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis of RA. TNF-α binds to its receptors to recruit certain molecules and forms two kinds of complexes (complex Ⅰ and Ⅱ) to regulate the pro-survival, apoptosis, and necrosis of cells. TNF-α upregulates RA by the methylation and acetylation of the RA synovial fibroblast gene and causes RA-derived joint damage through the induction of osteoclasts. Two TNF-α receptors mediate RA in opposite directions. TNF-α has been a target for the treatment of RA in which TNF-α inhibitors (TNFi) are administrated periodically for RA patients. Several mechanisms in the RA-related TNF-α signaling pathways remain imprecise including the regulation of regulatory T cells, osteoclast induction, and the potential interaction with the hypoxia-inducible factor. Further investigation into these questions may point out new methods for RA treatment to overcome the defects of current TNFi such as the anti-drug antibodies.

Suprapatellar Tibial Nailing: Future or Fad?

Over the last hundred years, there have been significant advancements in the way the Orthopaedic community treats tibial fractures. More recently, the focus of Orthopaedic trauma surgeons has been comparing the different techniques of insertion for tibial nails, specifically suprapatellar (SPTN) versus infrapatellar. The existing literature is convincing that there does not appear to be any clinically significant differences between suprapatellar and infrapatellar tibial nailing, with some apparent benefits of SPTN. Based on the current body of literature and our personal experience with SPTN, we believe the suprapatellar tibial nail will become the future for most tibial nailing procedures, regardless of fracture pattern. We have seen evidence of improved alignment in both proximal and distal fracture patterns, decreased radiation exposure and operative time, relaxation of the deforming forces, ease of imaging, and static positioning of the leg, which would be helpful for the unassisted surgeon, as well as no difference in anterior knee pain or articular damage within the knee between the two techniques.

Rat Bite Erosion of the Knee.

Erosive gout is a hallmark of severe disease and an indication to begin urate-lowering therapy, which can be started concurrently during a gout flare, to prevent further articular damage and flare recurrence.1 A 56-year-old male refugee presented to clinic with several days of left knee pain and swelling.

3D profiling of mouse epiphyses across ages reveals new potential imaging biomarkers of early spontaneous osteoarthritis.

Worldwide research groups and funding bodies have highlighted the need for imaging biomarkers to predict osteoarthritis (OA) progression and treatment effectiveness. Changes in trabecular architecture, which can be detected with non-destructive high-resolution CT imaging, may reveal OA progression before apparent articular surface damage. Here, we analysed the tibial epiphyses of STR/Ort (OA-prone) and CBA (healthy, parental control) mice at different ages to characterise the effects of mouse age and strain on multiple bony parameters. We isolated epiphyseal components using a semi-automated method, and measured the total epiphyseal volume; cortical bone, trabecular bone and marrow space volumes; mean trabecular and cortical bone thicknesses; trabecular volume relative to cortical volume; trabecular volume relative to epiphyseal interior (trabecular BV/TV); and the trabecular degree of anisotropy. Using two-way ANOVA (significance level ≤0.05), we confirmed that all of these parameters change significantly with age, and that the two strains were significantly different in cortical and trabecular bone volumes, and trabecular degree of anisotropy. STR/Ort mice had higher cortical and trabecular volumes and a lower degree of anisotropy. As the two mouse strains reflect markedly divergent OA predispositions, these parameters have potential as bioimaging markers to monitor OA susceptibility and progression. Additionally, significant age/strain interaction effects were identified for total epiphyseal volume, marrow space volume and trabecular BV/TV. These interactions confirm that the two mouse strains have different epiphyseal growth patterns throughout life, some of which emerge prior to OA onset. Our findings not only propose valuable imaging biomarkers of OA, but also provide insight into ageing 3D epiphyseal architecture bone profiles and skeletal biology underlying the onset and development of age-related OA in STR/Ort mice.

Identification and analysis of key microRNAs derived from osteoarthritis synovial fluid exosomes.

Identification and analysis of key microRNAs derived from osteoarthritis synovial fluid exosomes.

Worsening of Articular Tissue Damage as Defined by Semi-Quantitative MRI Is Associated With Concurrent Quantitative Cartilage Loss Over 24 Months.

To assess the association of worsening of magnetic resonance imaging (MRI) semi-quantitative (SQ) tissue features with concurrent change in quantitative (Q) cartilage thickness measurements over 24 months within the Foundation for the National Institutes of Health (FNIH) Biomarker Consortium study. In all, 599 participants were included. SQ assessment included cartilage damage, meniscal extrusion and damage, osteophytes, bone marrow lesions (BMLs), and effusion- and Hoffa-synovitis. Change in medial compartment Q cartilage thickness was stratified by concurrent ipsicompartmental SQ changes. Between-group comparisons were performed using analysis of covariance (ANCOVA) with adjustment for age, sex, and body mass index (BMI). Results were presented as adjusted mean difference. Knees with any increase in SQ cartilage scores in the medial compartment (n = 268) showed more Q cartilage loss compared to knees that remained stable (mean adjusted difference [MAD] = -0.16 mm, 95% confidence interval [CI]: [-0.19, -0.13] mm). Knees with any increase in meniscal extrusion in the medial compartment (n = 98) showed more Q cartilage loss than knees without (MAD = -0.18 mm, 95% CI: [-0.22, -0.14] mm. Comparable findings were seen for meniscal damage worsening. Regarding BMLs, an increase by one subregion resulted in a MAD of Q cartilage loss of -0.10 mm, 95% CI: [-0.14, -0.06] mm, while this effect almost tripled for change in two or more subregions. Increase in either effusion- and/or Hoffa-synovitis by one grade resulted in a MAD of -0.07 mm, 95% CI: [-0.10, -0.03] mm. Worsening of SQ cartilage damage, meniscal extrusion and damage, number of subregions affected by BML, maximum size of BMLs and worsening of effusion- and/or Hoffa synovitis is associated with increased Q cartilage loss.

Effects of TNF-α inhibition versus secukinumab on active ultrasound-confirmed enthesitis in psoriatic arthritis.

Enthesitis is a hallmark of psoriatic disease, but its clinical assessment is problematic in terms of diagnostic sensitivity and overlap with other comorbid conditions. Ultrasound is a useful tool that can give a more detailed assessment of enthesitis. Research demonstrates that those with persistent ultrasound entheseal disease are at risk of progressive articular damage. With limited data to guide choice between biologic therapy for psoriatic arthritis (PsA) patients, we wanted to assess the response of ultrasound-confirmed enthesitis to different forms of biologic therapies and study its utility in making more informed decisions. This was an open label observational study including patients aged ⩾18 years, who fulfil the classification criteria for PSA (CASPAR) and were due to commence on their first biologic therapy. The primary outcome was the change in MAdrid Sonographic Enthesitis Index (MASEI) score at 16 weeks of treatment. The MASEI score was also modified to assess the active elementary lesions (ActiveMASEI). In all, 80 PsA patients were enrolled with 75 patients completing the study [secukinumab n = 23 and tumour necrosis factor inhibitor (TNFi) n = 52]. The mean reduction in MASEI score after 16 weeks of treatment was 3.42 with TNFi versus 1.74 with secukinumab (p = 0.097). There was a significant difference in the change in the MASEIActive score for TNFi versus secukinumab (4.37 versus 2.26; p = 0.030) and this difference was more pronounced when only power Doppler signal within 2 mm of the enthesis insertion was included (4.37 versus 2.00; p = 0.007). Clinical outcomes were similar for both classes of biologic apart from a significant reduction in regards to the Dermatology Life Quality Index and Psoriasis Area and Severity Index score with secukinumab versus TNFi. We have for the first time compared the effect of ultrasound-confirmed enthesitis between different forms of biologic therapies for PsA. We have seen an overall improvement in entheseal scores for both classes of medications and demonstrated a larger reduction in active entheseal disease for TNFi versus secukinumab that merits further exploration.

Transglutaminase 2 inhibitors attenuate osteoarthritic degeneration of TMJ-osteoarthritis by suppressing NF-κB activation.

The temporomandibular joint osteoarthritis (TMJ-OA) is characterized by progressive cartilage degradation, subchondral bone erosion, and chronic pain, leading to articular damage and chewing dysfunction. Studies have shown that interleukin-1β (IL-1β) plays a critical role in the development of TMJ-OA. Transglutaminase 2 (TG2) has been identified as a marker of chondrocyte hypertrophy and IL-1β was able to increase TG2 expression in chondrocytes. Therefore, the aim of this study was to explore the ability of TG2 inhibitors to suppress TMJ-OA progression. Firstly, toluidine blue staining, cell counting kit-8 assay, immunocytofluorescent staining and western blot were used to investigate the anti-inflammatory effects of TG2 inhibitors in IL-1β-stimulated murine chondrocytes and the underlying mechanisms. Afterwards, micro-CT analysis, histological staining, immunohistochemical and immunohistofluorescent staining were used to evaluate the therapeutic efficacy of TG2 inhibitors in monosodium iodoacetate (MIA)-induced TMJ-OA in rats. TG2 inhibitors suppressed the IL-1β-induced upregulation of COX-2, iNOS, MMP-13, and MMP-3 and reversed the IL-1β-induced proteoglycan loss in chondrocytes through inhibiting NF-κB activation. Consistently, the MIA-induced upregulation of MMP-13 and MMP-3, and loss of structural integrity of the articular cartilage and subchondral bone were markedly reversed by TG2 inhibitors via inhibiting NF-κB activation. TG2 inhibitors demonstrated a potent therapeutic efficacy on cartilage and subchondral bone structures of TMJ-OA by reducing inflammation and cartilage degradation through suppressing NF-κB activation.