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TDAG8 activation inhibits osteoclastic bone resorption
Author(s) -
Hikiji Hisako,
Endo Daisuke,
Horie Kyoji,
Harayama Takeshi,
Akahoshi Noriyuki,
Igarashi Hidemitsu,
Kihara Yasuyuki,
Yanagida Keisuke,
Takeda Junji,
Koji Takehiko,
Shimizu Takao,
Ishii Satoshi
Publication year - 2014
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.13-233106
Subject(s) - bone resorption , osteoclast , bone remodeling , receptor , osteoporosis , endocrinology , medicine , chemistry , microbiology and biotechnology , bone marrow , bone mineral , biology
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.—Hikiji, H., Endo, D., Horie, K., Harayama, T., Akahoshi, N., Igarashi, H., Kihara, Y., Yanagida, K., Takeda, J., Koji, T., Shimizu, T., Satoshi, I. TDAG8 activation inhibits osteoclastic bone resorption. FASEB J. 28, 871–879 (2014). www.fasebj.org