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The calcium sensing receptor is directly involved in both osteoclast differentiation and apoptosis
Author(s) -
Mentaverri R.,
Yano S.,
Chattopadhyay N.,
Petit L.,
Kifor O.,
Kamel S.,
Terwilliger E. F.,
Brazier M.,
Brown E. M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6304fje
Subject(s) - osteoclast , microbiology and biotechnology , rankl , signal transduction , protein kinase c , phospholipase c , chemistry , apoptosis , calcium in biology , kinase , intracellular , receptor , biology , activator (genetics) , biochemistry
Intracellular transduction pathways that are dependent on activation of the CaR by Ca o 2+ have been studied extensively in parathyroid and other cell types, and include cytosolic calcium, phospholipases C, A 2 , and D, protein kinase C isoforms and the cAMP/protein kinase A system. In this study, using bone marrow cells isolated from CaR −/− mice as well as DN‐CaR‐transfected RAW 264.7 cells, we provide evidence that expression of the CaR plays an important role in osteoclast differentiation. We also establish that activation of the CaR and resultant stimulation of PLC are involved in high Ca o 2+ ‐induced apoptosis of mature rabbit osteoclasts. Similar to RANKL, Ca o 2+ (20 mM) appeared to trigger rapid and significant nuclear translocation of NF‐κB in a CaR‐ and PLC‐dependent manner. In summary, our data suggest that stimulation of the CaR may play a pivotal role in the control of both osteoclast differentiation and apoptosis in the systems studied here through a signaling pathway involving activation of the CaR, phospholipase C, and NF‐κB.— Mentaverri, R., Yano, S., Chattopadhyay, N., Petit, L., Kifor, O., Kamel, S., Terwilliger, E. F., Brazier, M., Brown, E. M. The calcium sensing receptor is directly involved in both osteoclast differentiation and apoptosis. FASEB J. 20, E1945‐E1954 (2006)