Deficiencies of Homer2 and Homer3 accelerate aging-dependent bone loss in mice
강정윤, 강남주, 신동민, 양유미,
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강정윤 ( Kang Jung-Yun ) - Yonsei University College of Dentistry Department of Oral Biology
강남주 ( Kang Nam-Ju ) - Yonsei University College of Dentistry Department of Oral Biology
신동민 ( Shin Dong-Min ) - Yonsei University College of Dentistry Department of Oral Biology
양유미 ( Yang Yu-Mi ) - Yonsei University College of Dentistry Department of Oral Biology
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 interactionwith calcineurin, which then acted to regulate receptor activator of nuclear factor-kappa B ligand (RANKL)-inducedosteoclastogenesis and bone metabolism. However, to date, the role of Homers in osteoclastogenesis remainsunknown. 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 inbone density was not seen in mice with Homer2 (Homer2?/?) and Homer3 (Homer3?/?) deletion. Moreover, RANKLtreatment of bone marrow-derived monocytes/macrophages in Homer2/3 DKO mice significantly increased theformation of multinucleated cells and resorption areas. Finally, Homer2/3 DKO mice decreased bone density in anaging-dependent manner. These findings suggest a novel potent mode of bone homeostasis regulation throughosteoclasts differentiation during aging by Homer proteins, specifically Homer2 and Homer3.
키워드
Osteoclastogenesis; Homer scaffolding proteins; Osteoporosis; Aging
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