Deficiencies of Homer2 and Homer3 accelerate aging-dependent bone loss in mice
10.11620/IJOB.2020.45.3.126
- Author:
Jung Yun KANG
1
;
Namju KANG
;
Dong Min SHIN
;
Yu-Mi YANG
Author Information
1. Department of Oral Biology, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
- Publication Type:Original Article
- From:International Journal of Oral Biology
2020;45(3):126-133
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Homer proteins are scaffold proteins that regulate calcium (Ca2+) signaling by modulating the activity of multiple Ca2+ signaling proteins. In our previous report, Homer2 and Homer3 regulated NFATc1 function through its interaction with calcineurin, which then acted to regulate receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone metabolism. However, to date, the role of Homers in osteoclastogenesis remains unknown. In this study, we investigated the roles of Homer2 and Homer3 in aging-dependent bone remodeling. Deletion of Homer2/Homer3 (Homer2/3 DKO) markedly decreased the bone density of the femur. The decrease in bone density was not seen in mice with Homer2 (Homer2−/−) and Homer3 (Homer3−/−) deletion. Moreover, RANKL treatment of bone marrow-derived monocytes/macrophages in Homer2/3 DKO mice significantly increased the formation of multinucleated cells and resorption areas. Finally, Homer2/3 DKO mice decreased bone density in an aging-dependent manner. These findings suggest a novel potent mode of bone homeostasis regulation through osteoclasts differentiation during aging by Homer proteins, specifically Homer2 and Homer3.
