title: Conditional inactivation of Blimp1 in adult mice promotes increased bone mass.
abstract: Bone resorption, which is regulated by osteoclasts, is excessively activated in bone destructive diseases such as osteoporosis. Thus, controlling osteoclasts would be an effective strategy to prevent pathological bone loss. Although several transcription factors that regulate osteoclast differentiation and function could serve as molecular targets to inhibit osteoclast formation, those factors have not yet been characterized using a loss of function approach in adults. Here we report such a study showing that inactivation of B-lymphocyte induced maturation protein 1 (Blimp1) in adult mice increases bone mass by suppressing osteoclast formation. Using an ex vivo assay, we show that osteoclast differentiation is significantly inhibited by Blimp1 inactivation at an early stage of osteoclastogenesis. Conditional inactivation of Blimp1 inhibited osteoclast formation and increased bone mass in both male and female adult mice. Bone resorption parameters were significantly reduced by Blimp1 inactivation in vivo. Blimp1 reportedly regulates immune cell differentiation and function, but we detected no immune cell failure following Blimp1 inactivation. These data suggest that Blimp1 is a potential target to promote increased bone mass and prevent osteoclastogenesis.
authors: Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors: Yoshiteru
authors: Y
authors: Miyauchi
authors: Hiroya
authors: H
authors: Miyamoto
authors: Shigeyuki
authors: S
authors: Yoshida
authors: Tomoaki
authors: T
authors: Mori
authors: Hiroya
authors: H
authors: Kanagawa
authors: Eri
authors: E
authors: Katsuyama
authors: Atsuhiro
authors: A
authors: Fujie
authors: Wu
authors: W
authors: Hao
authors: Hiroko
authors: H
authors: Hoshi
authors: Kana
authors: K
authors: Miyamoto
authors: Yuiko
authors: Y
authors: Sato
authors: Tami
authors: T
authors: Kobayashi
authors: Haruhiko
authors: H
authors: Akiyama
authors: Hideo
authors: H
authors: Morioka
authors: Morio
authors: M
authors: Matsumoto
authors: Yoshiaki
authors: Y
authors: Toyama
authors: Takeshi
authors: T
authors: Miyamoto
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism*; D001842:Bone and Bones / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D010010:Osteoclasts / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1