Deficiencies of Homer2 and Homer3 accelerate aging-dependent bone loss in mice

• Published in: International journal of oral biology Vol. 45; no. 3; pp. 126 - 133
• Main Authors: Kang, Jung Yun, Kang, Namju, Shin, Dong Min, Yang, Yu-Mi
• Format: Journal Article
• Language: Korean
• Published: 대한구강생물학회 30.09.2020
• Subjects: 치의학; Osteoclastogenesis; Aging; Osteoporosis; Homer scaffolding proteins
• ISSN: 1226-7155; 2287-6618

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.