Lectin-like oxidized low density lipoprotein receptor 1-deficient mice show resistance to instability-induced osteoarthritis

Abstract

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.

Acknowledgements

We thank Katsumi Okumoto (Department of Life Science Institute, Kindai University Faculty of Medicine) and Yuta Onodera (Division of Cell Biology for Regenerative Medicine, Faculty of Medicine, Kindai University) for providing technical assistance in this study.