International Journal of Oral Biology

  • 제45권3호
  • /
  • Pages.126-133
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  • 2020
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  • 1226-7155(pISSN)
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  • 2287-6618(eISSN)
대한구강생물학회 (The Korean Academy of Oral Biology)
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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)
  • 투고 : 2020.08.10
  • 심사 : 2020.08.20
  • 발행 : 2020.09.30
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초록

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.

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