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

摘要

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~(-1-)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.