Anti-apoptotic Molecule Bcl-2 Regulates the Differentiation, Activation, and Survival of Both Osteoblasts and Osteoclasts

Nagase, Y; Iwasawa, M; Akiyama, T; Kadono, Y; Nakamura, M; Oshima, Y; Yasui, T; Matsumoto, T; Hirose, J; Nakamura, H; Miyamoto, T; Bouillet, P; Nakamura, K; Tanaka, S

Author(s): Nagase, Y; Iwasawa, M; Akiyama, T; Kadono, Y; Nakamura, M; Oshima, Y; Yasui, T; Matsumoto, T; Hirose, J; Nakamura, H; Miyamoto, T; Bouillet, P; Nakamura, K; Tanaka, S;
Details: Publication Year 2009-12-25,Volume 284,Issue #52,Page 36659-36669
Journal Title: JOURNAL OF BIOLOGICAL CHEMISTRY
Publication Type: Journal Article
Abstract: The anti-apoptotic 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. Bcl-2(-/-) mice are growth-retarded and exhibit increased bone volume of the primary spongiosa, mainly due to the decreased number and dysfunction of osteoclasts. Osteoblast function is also impaired in Bcl-2(-/-) mice. Ex vivo studies on osteoblasts and osteoclasts showed that Bcl-2 promoted the differentiation, activation, and survival of both cell types. Because Bcl-2(-/-) mice die before 6 weeks of age due to renal failure and cannot be compared with 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. Loss of a single Bim allele restored normal osteoclast function in Bcl-2(-/-) mice but did not restore the impaired function of osteoblasts, and the mice exhibited osteopenia. These data demonstrate that Bcl-2 promotes the differentiation, activity, and survival of both osteoblasts and osteoclasts. The balance between Bcl-2 and Bim regulates osteoclast apoptosis and function, whereas other pro-apoptotic members are important for osteoblasts.
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Keywords: SRC KINASE-ACTIVITY; CELL-DEATH; SKELETAL DEVELOPMENT; TARGETED DISRUPTION; SIGNALING PATHWAY; IMMUNE-SYSTEM; BONE-CELLS; B-CELLS; C-SRC; EXPRESSION
Publisher's Version: https://doi.org/10.1074/jbc.M109.016915
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-12-25 12:00:00