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

Authors
 Yu-Mi Yang  ;  Min Seuk Kim  ;  Aran Son  ;  Jeong Hee Hong  ;  Kyung-Ho Kim  ;  Jeong Taeg Seo  ;  Syng-Ill Lee  ;  Dong Min Shin 
Citation
 JOURNAL OF BONE AND MINERAL RESEARCH, Vol.24(10) : 1763-1769, 2009 
Journal Title
 JOURNAL OF BONE AND MINERAL RESEARCH 
ISSN
 0884-0431 
Issue Date
2009
MeSH
Animals ; Bone Density/drug effects ; Bone Marrow Cells/cytology ; Calcium Signaling/drug effects ; Cells, Cultured ; Mice ; Monocytes/drug effects ; Monocytes/enzymology ; Monocytes/pathology ; NFATC Transcription Factors/metabolism ; Osteoclasts/drug effects* ; Osteoclasts/enzymology* ; Osteoclasts/pathology ; Osteogenesis/drug effects* ; Osteopetrosis/enzymology ; Osteopetrosis/pathology ; Osteopetrosis/physiopathology ; Protein Transport/drug effects ; RANK Ligand/pharmacology* ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/deficiency* ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
Keywords
sarco/endoplasmic reticulum Ca2+ATPase ; RANKL ; oste oclastogenesis ; [Ca2+]i oscillation ; osteopetrosis
Abstract
RANKL is essential for the terminal differentiation of monocytes/macrophages into osteoclasts. RANKL induces long-lasting oscillations in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) only after 24 h of stimulation. These Ca(2+) oscillations play a switch-on role in NFATc1 expression and osteoclast differentiation. Which Ca(2+) 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 Ca(2+) ATPase type 2 (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 [Ca(2+)](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 [Ca(2+)](i) oscillations that are essential for osteoclastogenesis.
Full Text
http://onlinelibrary.wiley.com/doi/10.1359/jbmr.090420/abstract
DOI
10.1359/jbmr.090420
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Orthodontics (교정과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Ho(김경호) ORCID logo https://orcid.org/0000-0002-8154-2041
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
Son, Seung Hwa(손승화)
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Lee, Syng Ill(이승일)
Hong, Jeong Hee(홍정희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104316
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