Effects of Etanercept on Experimental Osteoarthritis in Rats: Role of Histone Deacetylases.

IF 2.7 4区医学 Q1 ORTHOPEDICS

CARTILAGE Pub Date : 2024-07-26 DOI:10.1177/19476035241264012

Zhi-Hong Wen, Chi-Chieh Tang, Yen-You Lin, Zhi-Kang Yao, Shih-Peng Hsieh, Gar-Hwa-Lai, Wu-Fu Chen, Yen-Hsuan Jean

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引用次数: 0

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Etanercept 对大鼠实验性骨关节炎的影响：组蛋白去乙酰化酶的作用

目的：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）动物模型中软骨的破坏。肿瘤坏死因子（TNF）-α阻断剂治疗 OA 可减缓关节损伤，从而有效保护关节。目的：研究腹腔注射依那西普（TNF-α抑制剂）对大鼠OA发生的影响，以及大鼠痛觉行为和软骨中HDACs、RUNX2和MMP13表达的变化：通过前十字韧带横断（ACLT）诱导 Wistar 大鼠发生 OA。前交叉韧带断裂（ACLT）后连续5周腹腔注射1或5毫克依那西普（etanercept），分为ACLT+依那西普（1和5毫克/千克）组。对痛觉行为和膝关节宽度的变化进行了分析。对软骨进行组织学和免疫组化评估：结果：与单用 ACLT 相比，ACLT + etanercept 能明显改善机械异感和负重分布。在接受依那西普治疗的 OA 大鼠中，软骨退化和滑膜炎明显少于 ACLT 大鼠。受OA影响的软骨还显示，HDAC 6、7、RUNX-2和MMP-13的表达对依那西普的反应有所降低，但HDAC4的表达有所增加：我们的研究表明，依那西普治疗(1)减轻了大鼠OA和滑膜炎的发展，(2)减少了痛觉，(3)调节了软骨细胞的新陈代谢，可能是通过抑制细胞HDAC6和HDAC7、RUNX2和MMP13以及增加HDAC4的表达。基于新的证据，etanercept可能具有治疗OA的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CARTILAGE ORTHOPEDICS-

CiteScore

6.90

自引率

7.10%

发文量

期刊介绍： CARTILAGE publishes articles related to the musculoskeletal system with particular attention to cartilage repair, development, function, degeneration, transplantation, and rehabilitation. The journal is a forum for the exchange of ideas for the many types of researchers and clinicians involved in cartilage biology and repair. A primary objective of CARTILAGE is to foster the cross-fertilization of the findings between clinical and basic sciences throughout the various disciplines involved in cartilage repair. The journal publishes full length original manuscripts on all types of cartilage including articular, nasal, auricular, tracheal/bronchial, and intervertebral disc fibrocartilage. Manuscripts on clinical and laboratory research are welcome. Review articles, editorials, and letters are also encouraged. The ICRS envisages CARTILAGE as a forum for the exchange of knowledge among clinicians, scientists, patients, and researchers. The International Cartilage Repair Society (ICRS) is dedicated to promotion, encouragement, and distribution of fundamental and applied research of cartilage in order to permit a better knowledge of function and dysfunction of articular cartilage and its repair.