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

作者：Nagase Yuichi; Iwasawa Mitsuyasu; Akiyama Toru; Kadono Yuho; Nakamura Masaki; Oshima Yasushi; Yasui Tetsuro; Matsumoto Takumi; Hirose Jun; Nakamura Hiroaki; Miyamoto Takeshi; Bouillet Philippe; Nakamura Kozo; Tanaka Sakae^*

来源：Journal of Biological Chemistry, 2009, 284(52): 36659-36669.

DOI：10.1074/jbc.M109.016915

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.

• 出版日期2009-12-25
• 单位河北医科大学