Department of Orthopedic Surgery, Daejeon St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Orthopedic Surgery, Uijeongbu Saint Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Biomolecules. 2024 Sep 21;14(9):1192. doi: 10.3390/biom14091192.
Cartilage, a critical tissue for joint function, often degenerates due to osteoarthritis (OA), rheumatoid arthritis (RA), and trauma. Recent research underscores necroptosis, a regulated form of necrosis, as a key player in cartilage degradation. Unlike apoptosis, necroptosis triggers robust inflammatory responses, exacerbating tissue damage. Key mediators such as receptor-interacting serine/threonine-protein kinase-1 (RIPK1), receptor-interacting serine/threonine-protein kinase-3(RIPK3), and mixed lineage kinase domain-like (MLKL) are pivotal in this process. Studies reveal necroptosis contributes significantly to OA and RA pathophysiology, where elevated RIPK3 and associated proteins drive cartilage degradation. Targeting necroptotic pathways shows promise; inhibitors like Necrostatin-1 (Nec-1), GSK'872, and Necrosulfonamide (NSA) reduce necroptotic cell death, offering potential therapeutic avenues. Additionally, autophagy's role in mitigating necroptosis-induced damage highlights the need for comprehensive strategies addressing multiple pathways. Despite these insights, further research is essential to fully understand necroptosis' mechanisms and develop effective treatments. This review synthesizes current knowledge on necroptosis in cartilage degeneration, aiming to inform novel therapeutic approaches for OA, RA, and trauma.
软骨是关节功能的关键组织，但常因骨关节炎（OA）、类风湿性关节炎（RA）和创伤而退化。最近的研究强调，坏死性凋亡是一种受调控的坏死形式，是软骨降解的关键因素。与细胞凋亡不同，坏死性凋亡会引发强烈的炎症反应，加重组织损伤。受体相互作用丝氨酸/苏氨酸蛋白激酶-1（RIPK1）、受体相互作用丝氨酸/苏氨酸蛋白激酶-3（RIPK3）和混合谱系激酶结构域样蛋白（MLKL）等关键介质在这一过程中起着至关重要的作用。研究表明，坏死性凋亡对 OA 和 RA 的病理生理学有重要贡献，其中 RIPK3 及其相关蛋白的升高会导致软骨降解。针对坏死性凋亡途径具有很大的潜力；抑制剂如 Necrostatin-1（Nec-1）、GSK'872 和 Necrosulfonamide（NSA）可减少坏死性凋亡细胞死亡，为潜在的治疗方法提供了可能。此外，自噬在减轻坏死性凋亡诱导的损伤中的作用突显了需要采用综合策略来解决多个途径。尽管有这些发现，但仍需要进一步研究以全面了解坏死性凋亡的机制并开发有效的治疗方法。本综述综合了目前关于软骨退化中坏死性凋亡的知识，旨在为 OA、RA 和创伤提供新的治疗方法。
