Alteration of RANKL-induced osteoclastogenesis in primary cultured osteoclasts from SERCA2+/- mice

Yu Mi Yang, Seuk Kim Min, Aran Son, Hee Hong Jeong, Kyung Ho Kim, Taeg Seo Jeong, Syng Ill Lee, Min Shin Dong

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

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 Ca 2+ 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) on 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 NFATc1 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.

Original languageEnglish
Pages (from-to)1763-1769
Number of pages7
JournalJournal of Bone and Mineral Research
Volume24
Issue number10
DOIs
Publication statusPublished - 2009 Oct

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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