Antiapoptotic molecule Bcl-2 is essential for the anabolic activity of parathyroid hormone in bone

Author(s): Nagase, Y; Iwasawa, M; Akiyama, T; Ogata, N; Kadono, Y; Nakamura, M; Oshima, Y; Yasui, T; Matsumoto, T; Masuda, H; Bouillet, P; Nakamura, K; Tanaka, S;
Journal Title: SKELETAL BIOLOGY AND MEDICINE
Publication Type: S
Abstract: 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.
Publisher: BLACKWELL PUBLISHING
Keywords: CELL-DEATH; SKELETAL DEVELOPMENT; APOPTOSIS; OSTEOBLAST; MICE; ACTIVATION; EXPRESSION; SURVIVAL; HAIR; BIM
Publisher's Version: https://doi.org/10.1111/j.1749-6632.2009.05209.x
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Creation Date: 2010-01-01 12:00:00