Accelerated Development of Aging-Associated and Instability-Induced Osteoarthritis in Osteopontin-Deficient Mice
Accelerated Development of Aging-Associated and Instability-Induced Osteoarthritis in Osteopontin-Deficient Mice
复制标题
DOI：
10.1002/art.24705
复制
发表时间：
2009-08-01
影响因子：
--
通讯作者：
Uede, Toshimitsu
中科院分区：
文献类型：
--
作者：
Matsui, Yuichiro;Iwasaki, Norimasa;Uede, Toshimitsu
Objective.探讨骨桥蛋白（OPN）在骨关节炎（OA）发生发展中的作用。使用OPN缺陷型（OPN-/-）和对照野生型（WT）小鼠产生不稳定诱导的和衰老相关的OA模型。还使用体外软骨降解模型来评估OPN对关节软骨蛋白多糖损失的影响。OPN缺乏加重了衰老相关和不稳定诱导的OA。在没有OPN的情况下，软骨组织的结构变化和蛋白多糖损失增加。骨桥蛋白缺乏还导致基质金属蛋白酶13（MMP-13）的诱导，其降解软骨基质蛋白II型胶原的主要组分。蛋白多糖的丢失和胶原降解酶MMP-13的诱导都促进了OA的发生。骨桥蛋白在不稳定性诱导的和衰老相关的自发性OA的进展中起关键作用。骨桥蛋白通过影响基质金属蛋白酶-13的表达和蛋白多糖的丢失，是软骨降解的关键内在调节因子。
Objective. To investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions.Methods. Both instability-induced and aging-associated OA models were generated using OPN-deficient (OPN-/-) and control wild-type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage.Results. OPN deficiency exacerbated both aging-associated and instability-induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP-13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen-degrading enzyme MMP-13 facilitated the development of OA.Conclusion. OPN plays a pivotal role in the progression of both instability-induced and aging-associated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP-13 expression and proteoglycan loss.