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http://dx.doi.org/10.11620/IJOB.2020.45.3.126

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

Kang, Jung Yun (Department of Oral Biology, Yonsei University College of Dentistry)
Kang, Namju (Department of Oral Biology, Yonsei University College of Dentistry)
Shin, Dong Min (Department of Oral Biology, Yonsei University College of Dentistry)
Yang, Yu-Mi (Department of Oral Biology, Yonsei University College of Dentistry)
Publication Information
International Journal of Oral Biology / v.45, no.3, 2020 , pp. 126-133 More about this Journal
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.
Keywords
Osteoclastogenesis; Homer scaffolding proteins; Osteoporosis; Aging;
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