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.

Introduction
Materials and Methods
    1. 재료
    2. 실험동물
    3. BMMs의 분리
    4. 골 밀도 및 골격 형태 분석
    5. Tartrate-resistant acid phosphatase 염색 분석(TRAPstain assay)
    6. 골 흡수율 측정(Pit assay)
    7. 실험자료의 통계 분석
Results
    1. 대조군과 유전자 제거 마우스들에서 골 밀도 변화 비교
    2. RANKL에 의한 파골세포 분화 활성 변화
    3. Homer2/3 DKO 마우스에서 노화에 따른 골 밀도 변화
Discussion
References

• Jung Yun Kang(Department of Oral Biology, Yonsei University College of Dentistry/BK21 PLUS Project, Yonsei University College of Dentistry)
• Namju Kang(Department of Oral Biology, Yonsei University College of Dentistry/BK21 PLUS Project, Yonsei University College of Dentistry)
• Dong Min Shin(Department of Oral Biology, Yonsei University College of Dentistry)
• Yu-Mi Yang(Department of Oral Biology, Yonsei University College of Dentistry) Correspondence to