title: Caveolin-1 regulates osteoclastogenesis and bone metabolism in a sex-dependent manner.
abstract: Lipid raft microdomains have important roles in various cellular responses. Caveolae are a specialized type of lipid rafts that are stabilized by oligomers of caveolin proteins. Here, we show that caveolin-1 (Cav-1) plays a crucial role in the regulation of osteoclastogenesis. We found that caveolin-1 was dramatically up-regulated by receptor activator of nuclear factor κB ligand (RANKL), the osteoclast differentiation factor. Knockdown of Cav-1 reduced osteoclastogenesis and induction of NFATc1, the master transcription factor for osteoclastogenesis, by RANKL. Consistent with the in vitro results, injection of caveolin-1 siRNA onto mice calvariae showed reduction in RANKL-induced bone resorption and osteoclast formation. Moreover, Cav-1(-/-) female mice had higher bone volume and lower osteoclast number compared with wild type mice. However, Cav-1(-/-) male mice had both osteoclast and osteoblast numbers higher than wild type mice with no difference in bone volume. The sex dependence in the effect of Cav-1 deficiency was partly attributed to decreased receptor activator of nuclear factor κB and increased cFms expression in osteoclast precursors of female and male mice, respectively. Taken together, these data demonstrate that Cav-1 has a complicated but critical role for osteoclastogenesis.
authors.affiliation: From the Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749, Korea.
authors.forename: Yong Deok
authors.initials: YD
authors.lastname: Lee
authors.affiliation: From the Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749, Korea.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Yoon
authors.affiliation: From the Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749, Korea.
authors.forename: Cheol Kyu
authors.initials: CK
authors.lastname: Park
authors.affiliation: From the Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749, Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Lee
authors.affiliation: From the Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749, Korea.
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.affiliation: From the Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University, 28 Yeongon-Dong, Chongno-Gu, Seoul 110-749, Korea hhbkim@snu.ac.kr.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics*; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008297:Male; D021962:Membrane Microdomains / Q000235:genetics / Q000378:metabolism; D051379:Mice; D050778:NFATC Transcription Factors / Q000096:biosynthesis; D010010:Osteoclasts / Q000737:chemistry / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D053245:RANK Ligand / Q000096:biosynthesis; D012727:Sex Characteristics
chemical_list: D051242:Caveolin 1; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse
keywords: Caveolae; Caveolin; Lipid Raft; Osteoblast; Osteoclast; RANK; cFms