Int J Oral Biol.  2020 Sep;45(3):126-133. 10.11620/IJOB.2020.45.3.126.

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

• Kang JY
• Kang N
• Shin DM
• Yang YM

• KMID: 2507078
• DOI: http://doi.org/10.11620/IJOB.2020.45.3.126

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.

Keyword

Osteoclastogenesis; Homer scaffolding proteins; Osteoporosis; Aging