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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anabolic Agents / pharmacology*
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Animals
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / physiology
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Bcl-2-Like Protein 11
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Bone Resorption / genetics
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Bone and Bones / drug effects*
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Bone and Bones / metabolism*
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Calcification, Physiologic / drug effects
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Calcification, Physiologic / genetics
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Male
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Membrane Proteins / genetics
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Membrane Proteins / physiology
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Metabolism / drug effects
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Metabolism / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Osteogenesis / drug effects
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Osteogenesis / genetics
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Parathyroid Hormone / pharmacology*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / physiology*
Substances
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Anabolic Agents
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Apoptosis Regulatory Proteins
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Membrane Proteins
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Parathyroid Hormone
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2