Wen Zhi-Hong, Tang Chi-Chieh, Lin Yen-You, Yao Zhi-Kang, Hsieh Shih-Peng, Chen Wu-Fu, Jean Yen-Hsuan
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.
Department of Early Childhood Education, National Pintung University, Pingtung, Taiwan.
Cartilage. 2024 Jul 26:19476035241264012. doi: 10.1177/19476035241264012.
Mounting evidence suggests that histone deacetylases (HDAC) inhibitors reduce cartilage destruction in animal models of osteoarthritis (OA). Tumor necrosis factor (TNF)-α-blocking treatment for OA may provide effective joint protection by slowing joint damage. To investigate the effects of intraperitoneal administration of etanercept (a TNF-α inhibitor) on OA development in rats and changes in the nociceptive behavior of rats and expression of HDACs, RUNX2, and MMP13 in cartilage.
Induction of OA in Wistar rats was accomplished through anterior cruciate ligament transection (ACLT). One or five milligrams (mg) of etanercept was administered intraperitoneally for 5 consecutive weeks after ACLT to the ACLT + etanercept (1 and 5 mg/kg) groups. Nociceptive behavior and changes in knee joint width were analyzed. Cartilage was evaluated histologically and immunohistochemically.
ACLT + etanercept significantly improved mechanical allodynia and weight-bearing distribution compared to ACLT alone. In OA rats treated with etanercept, cartilage degeneration and synovitis were significantly less pronounced than those in ACLT rats. OA-affected cartilage also showed reduced expression of HDAC 6, 7, RUNX-2, and MMP-13 in response to etanercept but increased expression of HDAC4.
Our study demonstrated that etanercept therapy (1) attenuated the development of OA and synovitis in rats, (2) reduced nociception, and (3) regulated chondrocyte metabolism, possibly by inhibiting cell HDAC6 and HDAC7, RUNX2, and MMP13 and increasing HDAC4 expression. Based on new evidence, etanercept may have therapeutic potential in OA.
越来越多的证据表明，组蛋白去乙酰化酶（HDAC）抑制剂可减少骨关节炎（OA）动物模型中的软骨破坏。肿瘤坏死因子（TNF）-α阻断治疗OA可能通过减缓关节损伤提供有效的关节保护。本研究旨在探讨腹腔注射依那西普（一种TNF-α抑制剂）对大鼠OA发展、大鼠伤害感受行为变化以及软骨中HDACs、RUNX2和MMP13表达的影响。
通过前交叉韧带横断术（ACLT）诱导Wistar大鼠患OA。ACLT术后，向ACLT + 依那西普（1和5 mg/kg）组连续5周腹腔注射1或5毫克依那西普。分析伤害感受行为和膝关节宽度变化。对软骨进行组织学和免疫组织化学评估。
与单纯ACLT相比，ACLT + 依那西普显著改善了机械性异常疼痛和负重分布。在接受依那西普治疗的OA大鼠中，软骨退变和滑膜炎明显比ACLT大鼠轻。受OA影响的软骨对依那西普的反应还表现为HDAC 6、7、RUNX-2和MMP-13表达降低，但HDAC4表达增加。
我们的研究表明，依那西普治疗（1）可减轻大鼠OA和滑膜炎的发展，（2）减轻伤害感受，（3）调节软骨细胞代谢，可能是通过抑制细胞HDAC6和HDAC7、RUNX2和MMP13并增加HDAC4表达。基于新的证据，依那西普可能对OA具有治疗潜力。
