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Antiapoptotic molecule Bcl‐2 is essential for the anabolic activity of parathyroid hormone in bone
Author(s) -
Nagase Yuichi,
Iwasawa Mitsuyasu,
Akiyama Toru,
Ogata Naoshi,
Kadono Yuho,
Nakamura Masaki,
Oshima Yasushi,
Yasui Tetsuro,
Matsumoto Takumi,
Masuda Hironari,
Bouillet Philippe,
Nakamura Kozo,
Tanaka Sakae
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05209.x
Subject(s) - anabolism , parathyroid hormone , endocrinology , medicine , apoptosis , anabolic agents , hormone , chemistry , osteoblast , bone remodeling , mitochondrion , biology , calcium , in vitro , biochemistry
The antiapoptotic molecule Bcl‐2 inhibits apoptosis by preventing cytochrome c release from mitochondria. Although several studies have indicated the importance of Bcl‐2 in maintaining skeletal integrity, the detailed cellular and molecular mechanisms remain elusive. Since Bcl‐2 −/− mice die before six weeks of age on account of renal failure and cannot be compared to adult wild‐type mice, we generated Bcl‐2 −/− Bim +/− mice, in which a single Bim allele was inactivated, and compared them with their Bcl‐2 +/− Bim +/− littermates. Bcl‐2 −/− Bim +/− mice grew normally, but exhibited decreased bone mass compared to Bcl‐2 +/− Bim +/− mice, mainly due to impaired osteoblast function. Interestingly, the anabolic effect of parathyroid hormone (PTH) was not observed in Bcl‐2 −/− Bim +/− mice. This data demonstrates that Bcl‐2 is indispensable for the anabolic activity of PTH in bone.