Articular Disease Research Articles

Latest Findings on NOD-Like Receptor Family Pyrin Domain Containing Protein 3 Inflammasome and Bone and Articular Diseases

Inflammasomes are important components of the innate immune system. They are assembled by cytoplasmic pattern recognition receptors and play a critical role in the pathogenesis and progression of various inflammatory diseases through regulating the release and activation of inflammatory cytokines and inducing cell prytosis. NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome has been widely studied and has been shown to be closely associated with cardiovascular diseases and metabolic disorders. Bone and joint diseases, such as osteoarthritis and rheumatoid arthritis show high prevalence worldwide and can cause bone and cartilage damage, pain, and dysfunction, adversely affecting the patients' quality of life. The reported findings of some studies indicate that the pathogenesis of various bone and articular diseases is associated with NLRP3 inflammasome. Small molecule antagonists targeting NLRP3 inflammasome have shown considerable therapeutic potentials, but their clinical application still needs further exploration. Herein, we reviewed the composition and function of NLRP3 inflammasome and its association with bone and articular diseases.

Overview on the Link Between the Complement System and Auto-Immune Articular and Pulmonary Disease.

Complement system (CS) dysregulation is a key factor in the pathogenesis of different autoimmune diseases playing a central role in many immune innate and adaptive processes. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by ta breach of self-tolerance leading to a synovitis and extra-articular manifestations. The CS is activated in RA and seems not only to mediate direct tissue damage but also play a role in the initiation of RA pathogenetic mechanisms through interactions with citrullinated proteins. Interstitial lung disease (ILD) represents the most common extra-articular manifestation that can lead to progressive fibrosis. In this review, we focused on the evidence of CS dysregulation in RA and in ILD, and highlighted the role of the CS in both the innate and adaptive immune responses in the development of diseases, by using idiopathic pulmonary fibrosis as a model of lung disease. As a proof of concept, we dissected the evidence that several treatments used to treat RA and ILD such as glucocorticoids, pirfenidone, disease modifying antirheumatic drugs, targeted biologics such as tumor necrosis factor (TNF)-inhibitors, rituximab, tocilizumab, and nintedanib may act indirectly on the CS, suggesting that the CS might represent a potential therapeutic target in these complex diseases.

Reply to the Letter to the Editor: Are the Pathologic Features of Enthesopathy, Tendinopathy, and Labral and Articular Disc Disease Related to Mucoid Degeneration? A Systematic Review.

1Associate Dean for Comprehensive Care, Dell Medical School, Department of Surgery and Perioperative Care, Austin, TX, USA D. Ring, Dell Medical School, Department of Surgery and Perioperative Care, Health Discovery Building 6 #706, 1701 Trinity Street, Austin, TX 78712, USA, Email: [email protected] (RE: Maffulli N. Letter to the Editor: Are the Pathologic Features of Enthesopathy, Tendinopathy, and Labral and Articular Disc Disease Related to Mucoid Degeneration? A Systematic Review Clin Orthop Relat Res. Published online 2023. DOI: 10.1097/CORR.0000000000002684.) The author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writer, and do not reflect the opinion or policy of CORR® or The Association of Bone and Joint Surgeons®.

Letter to the Editor: Are the Pathologic Features of Enthesopathy, Tendinopathy, and Labral and Articular Disc Disease Related to Mucoid Degeneration? A Systematic Review.

Letter to the Editor: Are the Pathologic Features of Enthesopathy, Tendinopathy, and Labral and Articular Disc Disease Related to Mucoid Degeneration? A Systematic Review.

Exosomes derived from bone marrow mesenchymal stem cells pretreated with decellularized extracellular matrix enhance the alleviation of osteoarthritis through miR-3473b/PTEN axis.

Osteoarthritis (OA) is a prevalent degenerative articular disease for which there is no effective treatment. Progress has been made in MSC-based therapy in OA, and the efficacy has been demonstrated to be due to paracrine exosomes from MSCs. Decellularized extracellular matrix (dECM) provides an optimum microenvironment for the expansion of MSCs. In this study, we aimed to investigate whether exosomes isolated from bone marrow mesenchymal stem cells (BMSCs) with dECM pretreatment (dECM-BMSC-Exos) enhance the amelioration of OA. Exosomes from BMSCs with or without dECM pretreatment were isolated. We measured and compared the effect of the BMSC-Exo and dECM-BMSC-Exo on IL-1β-induced chondrocytes by analyzing proliferation, anabolism and catabolism, migration and apoptosis in vitro. The in vivo experiment was performed by articular injection of exosomes into DMM mice, followed by histological evaluation of cartilage. miRNA sequencing of exosomes was performed on BMSC-Exo and dECM-BMSC-Exo to investigate the underlying mechanism. The function of miR-3473b was validated by the rescue studies in vitro and in vivo using antagomir-3473b. IL-1β-treated chondrocytes treated with dECM-BMSC-Exos showed enhanced proliferation, anabolism, migration and anti-apoptosis properties compared with BMSC-Exos. DMM mice injected with dECM-BMSC-Exo showed better cartilage regeneration than those injected with BMSC-Exo. Interestingly, miR-3473b was significantly elevated in dECM-BMSC-Exos and was found to mediate the protective effect in chondrocytes by targeting PTEN, which activated the PTEN/AKT signaling pathway. dECM-BMSC-Exo can enhance the alleviation of osteoarthritis via promoting migration, improving anabolism, and inhibiting apoptosis of chondrocytes by upregulating miR-3473b , which targets PTEN.

Marine-Inspired Approaches as a Smart Tool to Face Osteochondral Regeneration.

The degeneration of osteochondral tissue represents one of the major causes of disability in modern society and it is expected to fuel the demand for new solutions to repair and regenerate the damaged articular joints. In particular, osteoarthritis (OA) is the most common complication in articular diseases and a leading cause of chronic disability affecting a steady increasing number of people. The regeneration of osteochondral (OC) defects is one of the most challenging tasks in orthopedics since this anatomical region is composed of different tissues, characterized by antithetic features and functionalities, in tight connection to work together as a joint. The altered structural and mechanical joint environment impairs the natural tissue metabolism, thus making OC regeneration even more challenging. In this scenario, marine-derived ingredients elicit ever-increased interest for biomedical applications as a result of their outstanding mechanical and multiple biologic properties. The review highlights the possibility to exploit such unique features using a combination of bio-inspired synthesis process and 3D manufacturing technologies, relevant to generate compositionally and structurally graded hybrid constructs reproducing the smart architecture and biomechanical functions of natural OC regions.

Comparison between methotrexate and apremilast in Psoriatic Arthritis-a single blind randomized controlled trial (APREMEPsA study).

To compare the efficacy of methotrexate and apremilast in psoriatic arthritis (PsA). This Single blinded (physician), parallel group, randomized controlled trial was conducted at a single centre between October 2019 and December 2020. Adult PsA patients (age > 18years), fulfilling CASPAR criteria, not on methotrexate/apremilast in last 3months and never receiving bDMARDs or, JAK inhibitors, having active articular disease (one or more swollen joint or, having one or more tender entheseal point) were recruited. Primary outcome measure was rate of major cDAPSA response at week 24 and secondary outcome measures were ACR 20 response, change in PASI score, Maastricht enthesitis score, Leeds dactylitis index, and health assessment questionnaire-disability index (HAQ-DI) and number of adverse events at week 24 between methotrexate and apremilast groups. A total of 31 patients were recruited (15 in the apremilast arm and 16 in the methotrexate arm) amongst whom 26 patients completed 24weeks follow up (13 patients in the apremilast arm and 13 patients in the methotrexate arm). Median cDAPSA score at baseline was 23 (9) in the apremilast group and 20 (21) in the methotrexate group. No difference in major cDAPSA response at week 24 was observed between apremilast and methotrexate arm (20% vs. 37.5%; p = 0.433). In the secondary outcome measures, there was no significant differences between both the groups. Both the drugs were safe without any serious adverse events. There was no significant difference between methotrexate and apremilast in terms of efficacy as measured by cDAPSA and ACR20 responses.

Hydroquinone, an Environmental Pollutant, Affects Cartilage Homeostasis through the Activation of the Aryl Hydrocarbon Receptor Pathway.

Exposure to environmental pollutants has a proven detrimental impact on different aspects of human health. Increasing evidence has linked pollution to the degeneration of tissues in the joints, although through vastly uncharacterised mechanisms. We have previously shown that exposure to hydroquinone (HQ), a benzene metabolite that can be found in motor fuels and cigarette smoke, exacerbates synovial hypertrophy and oxidative stress in the synovium. To further understand the impact of the pollutant on joint health, here we investigated the effect of HQ on the articular cartilage. HQ exposure aggravated cartilage damage in rats in which inflammatory arthritis was induced by injection of Collagen type II. Cell viability, cell phenotypic changes and oxidative stress were quantified in primary bovine articular chondrocytes exposed to HQ in the presence or absence of IL-1β. HQ stimulation downregulated phenotypic markers genes SOX-9 and Col2a1, whereas it upregulated the expression of the catabolic enzymes MMP-3 and ADAMTS5 at the mRNA level. HQ also reduced proteoglycan content and promoted oxidative stress alone and in synergy with IL-1β. Finally, we showed that HQ-degenerative effects were mediated by the activation of the Aryl Hydrocarbon Receptor. Together, our findings describe the harmful effects of HQ on articular cartilage health, providing novel evidence surrounding the toxic mechanisms of environmental pollutants underlying the onset of articular diseases.

DEGENERATIVE ARTICULAR CARTILAGE DISEASE, OSTEOARTHROSIS

Introduction: Osteoarthrosis (OA), degenerative articular cartilage disease is a chronic inflammatory arthropathy involving joint elements (subchondral bone, synovial membrane, hyaline cartilage and others). It is due to a disorder in the regulation between degradation and synthesis of the extracellular matrix of cartilage, involving bone and synovial membrane in a biochemical process mediated by growth factors and cytokines which, in turn, intervene in the course of bone remodeling and joint destruction. Objective: to detail the current information related to osteoarthrosis, description, etiology, classification, imaging classification, management and current treatments. Methodology: a total of 52 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 38 bibliographies were used because the other articles were not relevant for this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: arthrosis, osteoartrose, bones, osteoartrosis, articular cartilage. Results: The prevalence of osteoarthrosis increases directly with age 25-35 years 0.1 % 35-65 years 30 % and over 80 years 80-100 %. An improvement of pain and sensitivity is observed with local treatment with capsaicin. Paracetamol can be considered as the basic analgesic in the treatment of most chronic osteoarticular pain in doses of 1 gram four times/day. Opioids have an analgesic effect that almost completely eliminates all kinds of pain regardless of its intensity or site of affection. Short-term and long-term parenteral corticosteroid use is effective in controlling pain and stiffness. Systemic use of corticosteroids in OA is not warranted and only intra-articular injections are advised. Diacerein decreases IL 1Beta production in cartilage as well as nitric oxide levels by antagonizing the catabolic process and stimulates the anabolic process of cartilage. Chondroitin sulfate does not present a clinically relevant effect on joint pain or joint space reduction. Conclusions: osteoarthritis should be considered as a chronic, irreversible and progressive lesion. There are factors that aggravate its prognosis. Many measures are recommended to the patient and his family, especially if it is an elderly patient, in order to avoid the progression of joint damage. Surgical treatment is reserved for patients with severe pain or marked deformity, which occurs in advanced OA. Among the most frequently used procedures are: valgus osteotomy of the proximal tibia, arthroplasty, arthrodesis and amniotic membrane implantation. Bone tissue regenerative currents using tetracyclines that prevent the activation of metalloproteases, autologous chondrocyte implants, hypoxia inducible factor (HIF-1/2a), parathyroid hormone that stimulates chondrocyte multiplication and the use of in situ stem cells, cartilage regeneration and a better understanding of the developmental protein ancestor of osteogenesis, will be part of the medical management protocol, being a promising therapy for future therapy. KEY WORDS: Osteoarthrosis, osteoartrose, bones, osteoartrosis, articular cartilage.

Cytokines in Spondyloarthritis and Inflammatory Bowel Diseases: From Pathogenesis to Therapeutic Implications.

Spondyloarthritis and inflammatory bowel diseases are chronic immune disorders of the joints and the gut that often coexist in the same patient, increasing the burden of each disorder, worsening patients' quality of life, and influencing therapeutic strategies. Genetic predisposition, environmental triggers, microbiome features, immune cell trafficking, and soluble factors such as cytokines contribute to the pathogenesis of both articular and intestinal inflammation. Most of the molecular targeted biological therapies developed over the last two decades were based on evidence that specific cytokines may be involved in these immune diseases. Despite pro-inflammatory cytokine pathways sharing the pathogenesis of both articular and gut diseases (i.e., tumor necrosis factor and interleukin-23), several other cytokines (i.e., interleukin-17) may be differently involved in the tissue damage process, depending on the specific disease and the organ involved in inflammation, making difficult the identification of a therapeutic plan that is efficacious for both inflammatory manifestations. In this narrative review, we comprehensively summarize the current knowledge on cytokine involvement in spondyloarthritis and inflammatory bowel diseases, underlining similarities and differences among their pathogenetic pathways; finally, we provide an overview of current and potential future treatment strategies to simultaneously target both articular and gut immune disorders.

P530 The Burden on Cohabitants of Patients with Inflammatory Bowel Disease: A Cross-Sectional Study

Abstract Background Inflammatory bowel disease is a chronic disease characterized by digestive symptoms with an increasing incidence and prevalence. It is well established its impact on the quality of life of patients and their main caregivers but no study has yet considered the consequences of IBD on cohabitants with no direct involvement in patient`s care. Our aims were to analyze quality of life in cohabitants of people with IBD and identify potential related factors. Methods We conducted a cross-sectional study that included patients with IBD and their house-hold members. Participants were recruited from a period of two months from patients attending the IBD unit of our hospital. Inclusion criteria were a definite diagnosis of IBD and household members living in the same house for a period of 1 year or more. Exclusion criteria were an age <18, refusal to participate or subjects unable to fulfill the questionnaires. Demographic data was obtained for patients and household members. IBD activity was assessed by using the Partial Mayo Score and the Harvey-Bradshaw score. Other relevant information regarding the prior and current state of the disease was collected. Quality of life was assessed in the case of the patients with the Inflammatory Bowel Disease Questionnaire (IBDQ-32) and for the household members we used the Household Members Quality of Life-Inflammatory Bowel Disease (HHMQoL-IBD) questionnaire. Results We included 22 patients with UC, 32 patients with CD and 2 patients with indeterminate colitis and 82 household members. Both groups had similar sociodemographic characteristics. The univariate analysis of the quality of life of cohabitants showed a significant association of HHMQoL-IBD and IBDQ-32 score in their relatives (p<0.0001) (Figure 1), last CRP (p=0.043), number of disease flares in the last year (p=0.04), extraintestinal diseases (p=0.01) and particularly articular disease (p=0.04). Cohabitants of patients with CD had significantly lower HHMQoL-IBD than UC ones (53 ± 18 vs. 62 ± 23; p=0.049). Among cohabitants of patients with UC and CD, patient’s CRP in the last control was related to HHMQoL-IBD score (p=0.043 and p=0.04 respectively). In a linear multiple regression analysis, IBDQ-32 score (p<0.0001) in patients and the presence of extraintestinal disease (p=0.048) were independent predictors of cohabitant’s quality of life, and particularly articular disease. Conclusion Quality of life in household members of patients with IBD is related to patient’s quality of life and extraintestinal conditions related to the disease. Our study shows how important is to analyze and act in the patient’s whole environment, taking into consideration not only clinical variables but also the relational conditions and impact of the disease.

P368 The presence of extra-intestinal manifestations is associated with poor prognosis in acute severe ulcerative colitis: A KASID multicenter study

Abstract Background Many patients with inflammatory bowel disease experience extra-intestinal manifestations (EIM)s. The presence of EIMs is related to disease activity. Acute severe ulcerative colitis (ASUC) is associated with a high inflammatory burden. However, there are insufficient studies on the relation between the presence of EIMs and the prognosis of exacerbation of ulcerative colitis. This study was conducted to elucidate the correlation between EIMs and ASUC. Methods We retrospectively included patients who were hospitalized at four tertiary medical centers for ASUC management between January 2015 to December 2020, and data on the underlying disease, disease activity, EIMs, colectomy, treatment method, and readmission due to ulcerative colitis aggravation were checked. Results A total of 145 patients (mean age 44.4 years, 68 women) were investigated. The initial partial Mayo score, the Mayo endoscopy sub-score, and the ulcerative colitis endoscopic severity index were 7.6±0.8%, 2.7±0.5, and 6.0±1.4%, respectively. EIMs were expressed in a total of 10.3% (15/145) of patients. The most common type of EIMs was the peripheral articular type (46.7%) followed by skin lesions (20%) and axial articular disease (13.3%). The group with EIMs was younger and had a higher proportion of women than the group without EIMs (39.4 versus 45 years, p=0.03), and had a longer duration of disease (5.8 versus 3.5 years, p=0.02). The Mayo endoscopic sub-score (2.9 vs. 2.7, p<0.01) and partial endoscopic score (7.9 vs. 7.6, p<0.01) were also higher in the EIMs group. The length of hospital stay was also longer in the EIMs group (25.5 days vs. 13.8 days, p<0.01). The response rate to initial treatment was lower in the EIMs group (71.4% vs. 95.5%, p<0.01), and more rescue therapy (28.6% vs. 4.5%, p<0.01) was performed. The rate of colectomy on admission was also higher in the group with EIMs (13.3% vs. 0.8%, p<0.01). Patients with EIMs showed a high tendency to visit the hospital for re-exacerbation of ulcerative colitis after discharge (p=0.07, HR 2.10 CI: 0.93 – 4.76). Conclusion EIMs were expressed in a total of 10.3% of patients with ASUC. The presence of EIMs suggested a poor prognosis in ASUC.

Gout: from Hippocrates till the modern time

Gout (podagra) is one of the most ancient articular diseases. Its accurate mechanisms and causes were delineated only during the last century. Major historical investigatory steps are described in relation to causality and pathogenesis of the disease from Hippocrates ages till the modern time. The newest genetic and epidemiologic aspects of the disease are presented in this article.

Inflammation, fibrosis and E1 glycoprotein persistence in joint tissue of patients with post-Chikungunya chronic articular disease.

Chikungunya chronic joint disease causes debilitating arthralgia, significantly impacting the quality of life of affected individuals. In this study, patients underwent clinical follow-ups, joint biopsies, and pre-biopsy and 24 months post-biopsy serum dosage of cytokines. All participants were female and had pain in 12 joints on average, with 41.17% exhibiting moderate disease activity. Histopathological analysis revealed collagen deposition. Indirect immunofluorescence detected the CHIKV glycoprotein E1 antigen, and an increase in cytokines. Persistent inflammation and ineffective antiviral immune responses leading to antigen persistence may contribute to chronic CHIKV arthritis.

Association of DVWA rs11718863 Gene Polymorphism with Knee Osteoarthritis in Iraqi Patients

Background: Osteoarthritis (OA) is a complex degenerative articular disease that has an ambiguous pathogeny because variant risk factors participate in the process of cartilage deterioration. Genetic factors may have a role in the onset and progression of OA. Objective: To investigate potential association between severity of knee OA (KOA) and Double von Willebrand factor A domains DVWA rs11718863 gene polymorphism. Methods: One hundred and twenty Iraqi patients diagnosed with KOA, aged (45 years and above) and sixty healthy people (control) at the same age range, with no family history of OA were evaluated at Al-Imamein Al-Kadhimein Medical City (Rheumatology Department). The degree of severity of KOA was assessed by clinical and radiographic assessment. DVWA rs11718863 genotyping was performed using DNA sequencing (Sanger’s method). Results: Two different genotypes wild homozygote (TT) genotype and heterozygote (AT) appeared by genotyping of DVWArs:11718863. Highly significant difference (p<0.001) was found in distribution of the two genotypes in the three study groupsl the genotype (TT) was more frequent in control group (95.0%). Also, high significant difference (p<0.001) was noted in the two alleles (A, T) frequencies between control group and KOA patients group giving odd ratio 6.437 with 95% confidence intervals of (1.93-21.42). Conclusion: Iraqi subjects carrying AT genotype of DVWA rs11718863 gene are mostly susceptible for developing of KOA and the allele A of Tyr169Asn polymorphism are more frequent in those patients indicating that allele A may be a risk factor of onset of this disease. Age and body mass index are considered risk factors of onset and progression of KOA. Keywords: Double von Willebrand factor A domains (DVWA), single nucleotide polymorphism (SNP), body mass index, Knee osteoarthritis, KOA Citation: Hasan NN, Alwasiti EA, Ahmed MH. Association of DVWA rs11718863 gene polymorphism with knee osteoarthritis in Iraqi patients. Iraqi JMS. 2022; 20(2): 207-216. doi: 10.22578/IJMS.20.2.7

Injectable Drug Delivery Systems for Osteoarthritis and Rheumatoid Arthritis.

Joint diseases are one of the most common causes of morbidity and disability worldwide. The main diseases that affect joint cartilage are osteoarthritis and rheumatoid arthritis, which require chronic treatment focused on symptomatic relief. Conventional drugs administered through systemic or intra-articular routes have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. Therefore, there is an urgent need to develop improved strategies for drug delivery, in particular, the use of micro- and nanotechnology-based methods. Encapsulation of therapeutic agents in delivery systems reduces drug efflux from the joint and protects against rapid cellular and enzymatic clearance following intra-articular injection. Consequently, the use of drug delivery systems decreases side effects and increases therapeutic efficacy due to enhanced drug retention in the intra-articular space. Additionally, the frequency of intra-articular administration is reduced, as delivery systems enable sustained drug release. This review summarizes various advanced drug delivery systems, such as nano- and microcarriers, developed for articular cartilage diseases.

Primary antibody deficiency-associated arthritis shares features with spondyloarthritis and enteropathic arthritis

ObjectiveThe clinical spectrum of primary antibody deficiencies (PADs) and especially common variable immunodeficiency (CVID) includes various autoimmune disorders. We studied the prevalence and the features of articular rheumatic disease in...

MiR-17-92 cluster in osteoarthritis: Regulatory roles and clinical utility.

Osteoarthritis (OA) is the most prevalent articular disease, especially in aged population. Caused by multi-factors (e.g., trauma, inflammation, and overloading), OA leads to pain and disability in affected joints, which decreases patients' quality of life and increases social burden. In pathophysiology, OA is mainly characterized by cartilage hypertrophy or defect, subchondral bone sclerosis, and synovitis. The homeostasis of cell-cell communication is disturbed as well in such pro-inflammatory microenvironment, which provides clues for the diagnosis and treatment of OA. MicoRNAs (miRNAs) are endogenous non-coding RNAs that regulate various processes via post-transcriptional mechanisms. The miR-17-92 cluster is an miRNA polycistron encoded by the host gene called MIR17HG. Mature miRNAs generated from MIR17HG participate in biological activities such as oncogenesis, neurogenesis, and modulation of the immune system. Accumulating evidence also indicates that the expression level of miRNAs in the miR-17-92 cluster is tightly related to the pathological processes of OA, such as chondrocyte apoptosis, extracellular matrix degradation, bone remodeling, and synovitis. In this review, we aim to summarize the roles of the miR-17-92 cluster in the underlying molecular mechanism during the development and progression of OA and shed light on the new avenue of the diagnosis and treatment of OA.

Predicting Factors Affecting Quality of Life After Total Knee or Hip Arthroplasty for Osteoarthritis Patients : A Literature Review

Osteoarthritis is the most prevalent articular disease, the most common non-inflammatory arthropathy, and the main cause of chronic impairment. The most popular reconstructive treatment to improve the management of diseases that failed to respond well to standard medical therapy is total hip or total knee arthropathy. After a total knee or hip replacement, a patients abilities to carry out daily tasks was referred to as their quality of life. The intended outcome of this literature review was to describe the patients quality of life following surgery from earlier, comparable studies. This evaluation of the research suggests that certain factors, including comorbidities, preoperative quality of life, age, gender, excess weight, ethnicity, and psychiatric status, can predict health-related quality of life.

Ebselen, an Active Seleno-Organic Compound, Alleviates Articular Cartilage Degeneration in a Rat Model of Knee Osteoarthritis.

Osteoarthritis (OA) is a prevalent articular disease mainly characterized by extracellular matrix degradation, apoptosis, and inflammation, which lead to cartilage destruction and abnormal bone metabolism. With undesirable side effects, current limited symptomatic treatments are aimed at relieving pain and improving joint mobility in patients with OA. Intra-articular (IA) hyaluronic acid (HA) injection, as a nonsurgical therapy, is commonly used in the clinical management of knee OA, but the efficacy of this therapeutic option remains controversial. Ebselen has tremendous pharmacological importance for some diseases due to its antioxidant, antiapoptotic, and anti-inflammatory features. However, there is no research examining the therapeutic effect of Ebselen in OA using the rat OA model. Therefore, we aimed to investigate the therapeutic effect of Ebselen on cartilage degeneration and its role in bone morphogenetic protein 2 (BMP2) and nuclear factor kappa B (NF-κB) signaling in the molecular pathogenesis of OA. We induced a knee OA model in rats with an IA injection of monosodium-iodoacetate (MIA). After the treatment of Ebselen, we evaluated its chondroprotective effects by morphological, histopathological, and immunohistochemical methods and an enzyme-linked immunosorbent assay. We report for the first time that Ebselen treatment alleviated articular cartilage degeneration in the rat knee OA model and reduced MIA-induced BMP2 and NF-κB expressions. In addition, our results unveiled that Ebselen decreased IL-β and IL-6 levels but did not affect COMP levels in the rat serum. Ebselen could be a promising therapeutic drug for the prevention and treatment of OA by alleviating cartilage degeneration and regulating BMP2 and NF-κB expressions.