Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)36659-36669
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number52
DOIs
Publication statusPublished - 2009 Dec 25

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Osteoblasts
Osteoclasts
Chemical activation
Molecules
Apoptosis
Mitochondria
Alleles
Cytochromes c
Bone
Metabolic Bone Diseases
Renal Insufficiency
Cell Survival
Bone and Bones
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts. / 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.

In: Journal of Biological Chemistry, Vol. 284, No. 52, 25.12.2009, p. 36659-36669.

Research output: Contribution to journalArticle

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 2009, 'Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts', Journal of Biological Chemistry, vol. 284, no. 52, pp. 36659-36669. https://doi.org/10.1074/jbc.M109.016915
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. / Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 52. pp. 36659-36669.
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