Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes controlling OA progression is poor. Here, we report the association of OA with increased levels of osteoclast-associated receptor (OSCAR), an immunoglobulin-like collagen-recognition receptor. In mice, OSCAR deletion abrogates OA manifestations, such as articular cartilage destruction, subchondral bone sclerosis, and hyaline cartilage loss. These effects are a result of decreased chondrocyte apoptosis, which is caused by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in induced OA. Treatments with human OSCAR-Fc fusion protein attenuates OA pathogenesis caused by experimental OA. Thus, this work highlights the function of OSCAR as a catabolic regulator of OA pathogenesis, indicating that OSCAR blockade is a potential therapy for OA.
|Publication status||Published - 2020 Dec 1|
Bibliographical noteFunding Information:
This work was supported by grants from the National Research Foundation of Korea funded by the Korea Government (MSIP) (no. 2017M3A9C8030537; no. 2017R1A6A3A11031928; no. 2019R1A5A6099645; and no. 2019R1A6C1010020). We would like to thank Yongwon Choi (University of Pennsylvania, USA) for helpful discussions and suggestions. We thank Jang-Soo Chun (GIST, South Korea) for discussions and help in in vitro studies.
© 2020, The Author(s).
All Science Journal Classification (ASJC) codes
- Physics and Astronomy(all)
- Biochemistry, Genetics and Molecular Biology(all)