Department of Biomedical Engineering, Department of Physiotherapy and Rehabilitation-Faculty of Health Sciences, Sakarya University of Applied Sciences, Sakarya, Turkey.
Department of Surgery, Faculty of Veterinary Medicine, Hatay Mustafa Kemal University, Hatay, Turkey.
Biol Trace Elem Res. 2023 Aug;201(8):3919-3927. doi: 10.1007/s12011-022-03472-4. Epub 2022 Nov 11.
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.
骨关节炎（OA）是一种常见的关节疾病，主要特征为细胞外基质降解、细胞凋亡和炎症，导致软骨破坏和异常骨代谢。由于目前的治疗方法有限，且存在不良反应，这些方法主要是为了缓解 OA 患者的疼痛和改善关节活动度。关节内（IA）透明质酸（HA）注射作为一种非手术治疗方法，常用于膝骨关节炎的临床管理，但这种治疗选择的疗效仍存在争议。由于具有抗氧化、抗凋亡和抗炎作用，依布硒啉在一些疾病中具有巨大的药理学重要性。然而，目前尚无研究使用大鼠 OA 模型来研究依布硒啉在 OA 中的治疗作用。因此，我们旨在研究依布硒啉对软骨退化的治疗作用及其在骨形态发生蛋白 2（BMP2）和核因子 kappa B（NF-κB）信号通路在 OA 分子发病机制中的作用。我们通过 IA 注射单碘乙酸（MIA）在大鼠中诱导膝骨关节炎模型。在依布硒啉治疗后，我们通过形态学、组织病理学和免疫组织化学方法以及酶联免疫吸附试验评估其软骨保护作用。我们首次报道依布硒啉治疗可减轻大鼠膝骨关节炎模型中的关节软骨退化，并降低 MIA 诱导的 BMP2 和 NF-κB 表达。此外，我们的结果还揭示，依布硒啉降低了大鼠血清中 IL-β 和 IL-6 的水平，但对 COMP 水平没有影响。依布硒啉可能通过减轻软骨退化和调节 BMP2 和 NF-κB 表达，成为预防和治疗 OA 的有前途的治疗药物。
