An Senbo, Hu Huiyu, Li Yusheng, Hu Yihe
1Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
2Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Aging Dis. 2020 Oct 1;11(5):1146-1157. doi: 10.14336/AD.2019.1127. eCollection 2020 Oct.
Recent studies have revealed novel forms of cell death beyond the canonical types of cellular apoptosis and necrosis, and these novel forms of cell death are induced by extreme microenvironmental factors. Pyroptosis, a type of regulated cell death, occurs when pattern recognition receptors (PRRs) induce the activation of cysteine-aspartic protease 1 (caspase-1) or caspase-11, which can trigger the release of the pyrogenic cytokines interleukin-1β (IL-1β) and IL-18. Osteoarthritis (OA), the most common joint disease worldwide, is characterized by low-grade inflammation and increased levels of cytokines, including IL-1β and IL-18. Additionally, some damaged chondrocytes associated with OA exhibit morphological changes consistent with pyroptosis, suggesting that this form of regulated cell death may contribute significantly to the pathology of OA. This review summarizes the molecular mechanisms of pyroptosis and shows the critical role of NLRP3 (NLR family, pyrin domain containing 3; NLR refers to "nucleotide-binding domain, leucine-rich repeat") inflammasomes. We also provide evidence describing potential role of pyroptosis in OA, including the relationship with OA risk factors and the contribution to cartilage degradation, synovitis and OA pain.
最近的研究揭示了除细胞凋亡和坏死等典型类型之外的新型细胞死亡形式，这些新型细胞死亡形式是由极端微环境因素诱导产生的。焦亡是一种程序性细胞死亡，当模式识别受体（PRRs）诱导半胱天冬酶-1（caspase-1）或半胱天冬酶-11激活时发生，这会触发促炎细胞因子白细胞介素-1β（IL-1β）和IL-18的释放。骨关节炎（OA）是全球最常见的关节疾病，其特征是低度炎症以及包括IL-1β和IL-18在内的细胞因子水平升高。此外，一些与OA相关的受损软骨细胞表现出与焦亡一致的形态学变化，这表明这种程序性细胞死亡形式可能在OA的病理过程中起重要作用。本综述总结了焦亡的分子机制，并展示了NLRP3（NLR家族，含pyrin结构域3；NLR指“核苷酸结合结构域，富含亮氨酸重复序列”）炎性小体的关键作用。我们还提供了证据描述焦亡在OA中的潜在作用，包括与OA危险因素的关系以及对软骨降解、滑膜炎和OA疼痛的影响。
