Antiapoptotic molecule Bcl-2 is essential for the anabolic activity of parathyroid hormone in bone.
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.
Nagase
Yuichi
Y
Department of Orthopaedic Surgery, University of Tokyo, Tokyo, Japan.
Iwasawa
Mitsuyasu
M
Akiyama
Toru
T
Ogata
Naoshi
N
Kadono
Yuho
Y
Nakamura
Masaki
M
Oshima
Yasushi
Y
Yasui
Tetsuro
T
Matsumoto
Takumi
T
Masuda
Hironari
H
Bouillet
Philippe
P
Nakamura
Kozo
K
Tanaka
Sakae
S
D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology; D000072224:Bcl-2-Like Protein 11; D001862:Bone Resorption / Q000235:genetics; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008660:Metabolism / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*
D045930:Anabolic Agents; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D010281:Parathyroid Hormone; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2