Lectin-like oxidized low density lipoprotein receptor 1-deficient mice show resistance to instability-induced osteoarthritis
Lectin-like oxidized low density lipoprotein receptor 1-deficient mice show resistance to instability-induced osteoarthritis
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DOI：
10.3109/03009742.2015.1135979
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发表时间：
2016-09-01
影响因子：
2.1
通讯作者：
Akagi, M.
中科院分区：
文献类型：
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作者：
Hashimoto, K.;Mori, S.;Akagi, M.
目的：氧化低密度脂蛋白（ox-LDL）受体1（LOX-1）/ox-LDL系统可能参与了骨关节炎（OA）的发生、发展，并参与了动脉粥样硬化的发病机制。然而，LOX-1/ox-LDL系统促进体内OA发展的机制尚不清楚。在这项研究中，我们研究了LOX-1/ox-LDL在OA的发展中的直接参与，通过使用LOX-1基因敲除（LOX-1（-）/（-））小鼠在关节不稳定诱导的OA模型。方法：在手术后4周和8周，在LOX-1（+）/（+）和LOX-1（-）/（-）小鼠中诱导膝关节不稳定，用组织学评分评估OA的发展。免疫组化分析用于评估LOX-1、ox-LDL、Runt相关转录因子2（Runx 2）和X型胶原（COL X）在关节软骨细胞和骨赘形成细胞中的表达。结果：在膝关节失稳模型中，LOX-1（-）/（-）小鼠膝关节症状明显减轻。LOX-1、ox-LDL、Runx 2和COL X在LOX-1（+）/（+）小鼠的关节软骨细胞和骨赘形成细胞中过表达，与LOX-1（+）/（+）小鼠相比，LOX-1（-）/（-）小鼠的关节软骨细胞和骨赘形成细胞中LOX-1、ox-LDL、Runx 2和COL X的表达显著下调。双重免疫染色表明LOX-1定位与Runx 2和COL X表达一致。结论：这些数据表明LOX-1/ox-LDL系统在通过软骨内成骨诱导的不稳定性OA的发病机制中发挥关键作用。LOX-1阳性软骨细胞和骨赘形成细胞可能是预防OA疾病进展的可能靶点。
Objectives: The lectin-like oxidized low density lipoprotein (ox-LDL) receptor 1 (LOX-1)/ox-LDL system, which contributes to the pathogenesis of atherosclerosis, may be involved in the development of osteoarthritis (OA). However, the mechanisms by which the LOX-1/ox-LDL system contributes to OA development in vivo are unclear. In this study, we investigated the direct involvement of LOX-1/ox-LDL in OA development by using LOX-1-knockout (LOX-1(-)/(-)) mice in a joint instability-induced model of OA.Method: OA development was evaluated with histological scoring at 4 and 8 weeks after surgery to induce knee destabilization in LOX-1(+)/(+) and Lox-1(-)/(-) mice. Immunohistological analysis was used to evaluate the expression of LOX-1, ox-LDL, Runt-related transcription factor 2 (Runx2), and type X collagen (COL X) in articular chondrocytes and osteophyte-forming cells. In addition, double immunofluorescence staining was performed to determine the relationships between LOX-1 and Runx2 or COL X expression.Results: In the model of knee destabilization, symptoms were significantly suppressed in LOX-1(-)/(-) mice. LOX-1, ox-LDL, Runx2, and COL X were overexpressed in articular chondrocytes and osteophyte-forming cells in LOX-1(+)/(+) mice and were significantly downregulated in articular chondrocytes and osteophyte-forming cells in LOX-1(-)/(-) mice compared with those in LOX-1(+)/(+) mice. Double immunostaining indicated that LOX-1 localization coincided with Runx2 and COL X expression.Conclusions: These data indicate that the LOX-1/ox-LDL system plays a pivotal role in the pathogenesis of instability induced OA through endochondral ossification. LOX-1-positive chondrocytes and osteophyte-forming cells may be possible targets to prevent disease progression in OA.