School of Biomedical Sciences, Kent State University, Kent, Ohio.
Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, Ohio.
J Cell Physiol. 2020 Oct;235(10):6366-6376. doi: 10.1002/jcp.29607. Epub 2020 Feb 4.
Accumulating evidence suggests that inflammation has a key role in the pathogenesis of osteoarthritis (OA). Nitric oxide (NO) has been established as one of the major inflammatory mediators in OA and drives many pathological changes during the development and progression of OA. Excessive production of NO in chondrocytes promotes cartilage destruction and cellular injury. The synthesis of NO in chondrocytes is catalyzed by inducible NO synthase (iNOS), which is thereby an attractive therapeutic target for the treatment of OA. A number of direct and indirect iNOS inhibitors, bioactive compounds, and plant-derived small molecules have been shown to exhibit chondroprotective effects by suppressing the expression of iNOS. Many of these iNOS inhibitors hold promise for the development of new, disease-modifying therapies for OA; however, attempts to demonstrate their success in clinical trials are not yet successful. Many plant extracts and plant-derived small molecules have also shown promise in animal models of OA, though further studies are needed in human clinical trials to confirm their therapeutic potential. In this review, we discuss the role of iNOS in OA pathology and the effects of various iNOS inhibitors in OA.
越来越多的证据表明，炎症在骨关节炎 (OA) 的发病机制中起着关键作用。一氧化氮 (NO) 已被确定为 OA 中的主要炎症介质之一，在 OA 的发展和进展过程中驱动许多病理变化。软骨细胞中过量的 NO 产生会促进软骨破坏和细胞损伤。软骨细胞中 NO 的合成由诱导型一氧化氮合酶 (iNOS) 催化，因此 iNOS 是治疗 OA 的一个有吸引力的治疗靶点。许多直接和间接的 iNOS 抑制剂、生物活性化合物和植物来源的小分子已被证明通过抑制 iNOS 的表达具有软骨保护作用。其中许多 iNOS 抑制剂有望为 OA 的新型疾病修饰疗法的发展提供帮助；然而，在临床试验中证明其成功的尝试尚未成功。许多植物提取物和植物来源的小分子在 OA 的动物模型中也显示出了希望，尽管需要在人类临床试验中进行进一步的研究来确认它们的治疗潜力。在这篇综述中，我们讨论了 iNOS 在 OA 病理中的作用以及各种 iNOS 抑制剂在 OA 中的作用。
