Shimasaki Miyako, Ueda Shusuke, Sakurai Masaru, Kawahara Norio, Ueda Yoshimichi, Ichiseki Toru
Department of Pathology 2, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku-gun 920-0293, Japan.
Department of Orthopaedic Surgery, Kanazawa Medical University, Daigaku 1-1, Uchinada-machi, Kahoku-gun 920-0293, Japan.
Biomolecules. 2024 Dec 20;14(12):1636. doi: 10.3390/biom14121636.
Inflammation and oxidative stress are crucial for osteoarthritis (OA) pathogenesis. Despite the potential of pharmacological pretreatment of chondrocytes in preventing OA, its efficacy in preventing the progression of cartilage damage and promoting its recovery has not been examined. In this study, an HO-induced human OA-like chondrocyte cell model was created using H1467 primary human chondrocytes to evaluate the efficacy of interleukin (IL)-6 and cyclooxygenase (COX)-2 inhibitors (tocilizumab and celecoxib, respectively) in the prevention and treatment of cartilage damage. HO significantly elevated the IL-6, COX-2, and matrix metalloproteinase (MMP)-13 levels. Although monotherapy decreased the levels, nuclear shrinkage and altered cell morphology, similar to those in the HO group, were observed. The expression of these factors was significantly lower in the combination therapy group, and the cell morphology was maintained. Moreover, the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was activated, and levels of the antioxidant protein heme oxygenase-1 (HO-1) were increased, especially in the combination group, indicating an anti-inflammatory effect. The treatment groups, particularly the combination group, demonstrated increased cell viability. Overall, the drug combination exhibited superior efficacy in preventing the progression of cartilage damage and promoted its recovery compared with the monotherapy. Given that the drugs herein are already in clinical use, they are suitable candidates for OA treatment.
炎症和氧化应激对骨关节炎（OA）的发病机制至关重要。尽管软骨细胞的药物预处理在预防OA方面具有潜力，但其在预防软骨损伤进展和促进其恢复方面的疗效尚未得到研究。在本研究中，使用H1467原代人软骨细胞建立了一种HO诱导的人OA样软骨细胞模型，以评估白细胞介素（IL）-6和环氧化酶（COX）-2抑制剂（分别为托珠单抗和塞来昔布）在预防和治疗软骨损伤中的疗效。HO显著提高了IL-6、COX-2和基质金属蛋白酶（MMP）-13的水平。虽然单一疗法降低了这些水平，但观察到细胞核收缩和细胞形态改变，类似于HO组。联合治疗组中这些因子的表达显著降低，并且细胞形态得以维持。此外，核因子红细胞2相关因子2（Nrf2）途径被激活，抗氧化蛋白血红素加氧酶-1（HO-1）的水平升高，尤其是在联合组中，表明具有抗炎作用。治疗组，特别是联合组，显示出细胞活力增加。总体而言，与单一疗法相比，药物联合在预防软骨损伤进展和促进其恢复方面表现出更优异的疗效。鉴于本文中的药物已在临床使用，它们是OA治疗的合适候选药物。
