ECTS2016 Poster Presentations Cell biology: osteoclasts and bone resorption (35 abstracts)
Yonsei University College of Dentistry, Seoul, Republic of Korea.
Ca2+ signaling and NFATc1 activation are essential for RANKL-induced osteoclast differentiation through the induction of Ca2+ oscillation, calcineurin activation, and translocation of NFATc1 into the nucleus. Homer proteins are scaffold proteins that have been proposed to modulate multiple Ca2+ signaling proteins, including inositol 1,4,5-triphosphate receptors, ryanodine receptors, transient receptor potential channels. In this study, we investigated the role of Homer2 and Homer3 in Ca2+ signaling during osteoclast differentiation using Homer2/Homer3 (Homer2/3) double-knockout (DKO) mice. Deletion of Homer2/3 markedly decreased the bone density of the tibias, resulting in bone erosion. Homer2/3 DKO bone marrow-derived monocytes/macrophages (BMMs) facilitated greatly osteoclast differentiation through increased NFATc1 expression and translocation of NFATc1 into the nucleus after 48 h of RANKL treatment. Notably, the interaction of Homer proteins with NFATc1 was inhibited by RANKL treatment, but restored by cyclosporine A treatment to inhibit calcineurin. Finally, RANKL treatment of Homer2/3 DKO BMMs significantly increased approximately threefold induction of multinucleated cells formation. These findings suggest that Homer2/3 regulate NFATc1 function by interacting with NFATc1 it in the cytosol and thus modulate the NFATc1 pathway and RANKL-induced osteoclast differentiation and bone metabolism. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2015R1A2A1A15054157) and (MOE) (2015R1D1A1A01057277).