Alteration of RANKL-Induced Osteoclastogenesis in Primary Cultured Osteoclasts From SERCA2( /-) Mice

作者：Yang Yu Mi; Kim Min Seuk; Son Aran; Hong Jeong Hee; Kim Kyung Ho; Seo Jeong Taeg; Lee Syng Ill; Shin Dong Min^*

来源：Journal of Bone and Mineral Research, 2009, 24(10): 1763-1769.

DOI：10.1359/JBMR.090420

• sarco/endoplasmic reticulum Ca2 ATPase
• RANKL
• osteoclastogenesis
• [Ca2 ](i) oscillation
• osteopetrosis

RANKL is essential for the terminal differentiation of monocytes/marcrophages into osteoclasts. RANKL induces long-lasting oscillations in the intracellular concentration of Ca2 ([Ca2 ](i)) only after 24 h of stimulation. These Ca2 oscillations play a switch-on role in NFATc1 expression and osteoclast differentiation. Which Ca2 transporting pathway is induced by RANKL to evoke the Ca2 oscillations and its specific role in RANKL-mediated osteoclast differentiation is not known. This study examined the effect of a partial loss of sarco/endoplasmic reticulum Ca2 ATPase type2 (SERCA2) oil osteoclast differentiation in SERCA2 heterozygote mice (SERCA2( /-)). The BMD in the tibias of SERCA2( /-) mice increased >1.5-fold compared with wildtype mice (WT). RANKL-induced [Ca2 ](i) oscillations were generated 48 h after RANKL treatment in the WT mice but not in the SERCA2( /-) bone marrow-derived macrophages (BMMs). Forty-eight hours after RANKL treatment, there was a lower level of NFATc1 protein expression and markedly reduced translocation of NFATcl. into the nucleus during osteoclastogenesis of the SERCA2( /-) BMMs. In addition, RANKL treatment of SERCA2( /-) BMMs incompletely induced formation of multinucleated cells, leading to reduced bone resorption activity. These results suggest that RANKL-mediated induction of SERCA2 plays a critical role in the RANKL-induced [Ca2 ](i) oscillations that are essential for osteoclastogenesis. J Bone Miner Res 2009;24:1763-1769. Published online on April 27, 2009; doi: 10.1359/JBMR.090420

• 出版日期2009-10