Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis.
Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis.
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DOI：
10.3390/ijms161125943
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发表时间：
2015-10-30
影响因子：
5.6
通讯作者：
Kim HA
中科院分区：
文献类型：
--
作者：
Hwang HS;Kim HA
细胞凋亡是一个高度调控的、活跃的细胞死亡过程，参与发育、动态平衡和衰老。细胞凋亡的失调会导致病理状态，如癌症、发育异常和退行性疾病。骨关节炎是老年人群中最常见的慢性关节疾病，其特征是关节软骨进行性破坏，导致严重的残疾。由于关节软骨完全依赖其驻留的细胞--软骨细胞来维持细胞外基质，软骨细胞的功能和生存能力的受损将导致关节软骨的衰竭。软骨下骨在维持正常软骨基质中的作用也已被提出，并提出关节软骨和软骨下骨在维持关节完整性和生理方面相互作用。一些研究人员将关节软骨和软骨下骨作为修复关节退变的靶点。在晚期骨性关节炎中，软骨细胞减少，通常伴有腔隙排空，这被认为是软骨细胞死亡是骨性关节炎进展的中心特征的证据。细胞凋亡明显存在于骨关节病软骨中，但软骨细胞凋亡在骨性关节炎发病机制中的相对作用尚不清楚，关于骨关节病软骨细胞凋亡率的报道也相互矛盾。目前尚不清楚软骨细胞凋亡是软骨退变的诱因还是软骨破坏的副产品。软骨细胞死亡和基质丢失可能形成恶性循环，两者的进展相互加重，文献表明软骨损伤的程度与软骨细胞的凋亡有一定的相关性。由于目前治疗骨性关节炎的方法只针对症状起作用，并不能预防或治愈骨性关节炎，因此软骨细胞的凋亡将是调控软骨退变的有效靶点。
Apoptosis is a highly-regulated, active process of cell death involved in development, homeostasis and aging. Dysregulation of apoptosis leads to pathological states, such as cancer, developmental anomalies and degenerative diseases. Osteoarthritis (OA), the most common chronic joint disease in the elderly population, is characterized by progressive destruction of articular cartilage, resulting in significant disability. Because articular cartilage depends solely on its resident cells, the chondrocytes, for the maintenance of extracellular matrix, the compromising of chondrocyte function and survival would lead to the failure of the articular cartilage. The role of subchondral bone in the maintenance of proper cartilage matrix has been suggested as well, and it has been proposed that both articular cartilage and subchondral bone interact with each other in the maintenance of articular integrity and physiology. Some investigators include both articular cartilage and subchondral bone as targets for repairing joint degeneration. In late-stage OA, the cartilage becomes hypocellular, often accompanied by lacunar emptying, which has been considered as evidence that chondrocyte death is a central feature in OA progression. Apoptosis clearly occurs in osteoarthritic cartilage; however, the relative contribution of chondrocyte apoptosis in the pathogenesis of OA is difficult to evaluate, and contradictory reports exist on the rate of apoptotic chondrocytes in osteoarthritic cartilage. It is not clear whether chondrocyte apoptosis is the inducer of cartilage degeneration or a byproduct of cartilage destruction. Chondrocyte death and matrix loss may form a vicious cycle, with the progression of one aggravating the other, and the literature reveals that there is a definite correlation between the degree of cartilage damage and chondrocyte apoptosis. Because current treatments for OA act only on symptoms and do not prevent or cure OA, chondrocyte apoptosis would be a valid target to modulate cartilage degeneration.