Bone Abstracts

Bone remodeling and maintenance require a fine balance between bone formation of osteoblasts and resorption of osteoclasts. Therefore, various skeletal disorders cause by imbalanced differentiation and activities of these cells. RANKL (receptor activator of NF-kB ligand) induces Ca²⁺ oscillations and activates NFATc1 (nuclear factor of activated T cells i) during osteoclast differentiation. Although Ca²⁺ oscillations play a key role for osteoclastogenesis, the molecular identification of Ca²⁺ influx via mechanosensitive calcium channels located on the plasma membrane for the generation of Ca²⁺ oscillation are not well known. We investigated the expression and functional role of mechanosensitive TRP (transient receptor potential) channels on Ca²⁺ signaling during osteoclastogenesis in RAW264.7 and bone marrow macrophage (BMM) cells. Ca²⁺ oscillations and entry were changed by the over-expression of TRPC3 and TRPC6. Activation of these channels had effects on the expression of NFATc1, activation of ERK pathway, and regulation of osteoclast differentiation. These results suggest that mechanosensitive TRP channels play a key role in the Ca²⁺ signaling of osteoclastogenesis. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) (2012R1A1A2007673).