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Publication : TDAG8 activation inhibits osteoclastic bone resorption.

First Author  Hikiji H Year  2014
Journal  FASEB J Volume  28
Issue  2 Pages  871-9
PubMed ID  24221084 Mgi Jnum  J:210384
Mgi Id  MGI:5570988 Doi  10.1096/fj.13-233106
Citation  Hikiji H, et al. (2014) TDAG8 activation inhibits osteoclastic bone resorption. FASEB J 28(2):871-9
abstractText  Although the roles of acids in bone metabolism are well characterized, the function of proton-sensing receptors in bone metabolism remains to be explored. In this study, we evaluated the role of proton-sensing receptor T-cell death-associated gene 8 (TDAG8) in osteoclastic activity during bone loss after ovariectomy. Through observations of bone mineral content, we found that pathological bone resorption was significantly exacerbated in mice homozygous for a gene trap mutation in the Tdag8 gene. Furthermore, osteoclasts from the homozygous mutant mice resorbed calcium in vitro more than the osteoclasts from the heterozygous mice did. Impaired osteoclast formation under acidic conditions was ameliorated in cultures of bone marrow cells by Tdag8 gene mutation. Extracellular acidification changed the cell morphology of osteoclasts via the TDAG8-Rho signaling pathway. These results suggest that the enhancement of TDAG8 function represents a new strategy for preventing bone resorption diseases, such as osteoporosis.
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