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Ebselen, an Active Seleno-Organic Compound, Alleviates Articular Cartilage Degeneration in a Rat Model of Knee
Hamza Malik Okuyan1, Ziya Yurtal2, İhsan Karaboğa3
1Department of Biomedical Engineering, Department of Physiotherapy and Rehabilitation-Faculty of Health Sciences, Sakarya University of Applied Sciences, Sakarya, Turkey. hmokuyan@gmail.com.
Abstract:
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.
Insights
Ebselen shows promise in treating osteoarthritis (OA) by protecting cartilage and reducing inflammation. This study found Ebselen alleviates cartilage damage and key inflammatory markers in a rat OA model.
Area of Science:
- Biomedical Science
- Pharmacology
- Rheumatology
Background:
- Osteoarthritis (OA) is a degenerative joint disease causing cartilage destruction and pain.
- Current OA treatments offer limited relief and have side effects.
- Ebselen possesses antioxidant, antiapoptotic, and anti-inflammatory properties, but its effect on OA is unstudied.
Purpose of the Study:
- To investigate the therapeutic potential of Ebselen in a rat model of knee osteoarthritis.
- To evaluate Ebselen's effects on cartilage degeneration and its modulation of BMP2 and NF-κB signaling pathways.
Main Methods:
- A rat knee osteoarthritis model was induced using intra-articular monosodium-iodoacetate (MIA) injection.
- Ebselen treatment efficacy was assessed using morphological, histopathological, and immunohistochemical analyses.
- Serum levels of inflammatory cytokines (IL-1β, IL-6) and COMP were measured via ELISA.
Main Results:
- Ebselen treatment significantly alleviated articular cartilage degeneration in the MIA-induced OA rat model.
- Ebselen reduced the expression of bone morphogenetic protein 2 (BMP2) and nuclear factor kappa B (NF-κB).
- Ebselen decreased serum levels of IL-1β and IL-6, with no significant effect on COMP.
Conclusions:
- Ebselen demonstrates chondroprotective effects in experimental osteoarthritis.
- Ebselen may exert its therapeutic benefits by regulating BMP2 and NF-κB signaling pathways.
- Ebselen represents a potential therapeutic agent for osteoarthritis prevention and treatment.

