title: Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice.
abstract: A positive correlation between plasma levels of HDL and bone mass has been reported by epidemiological studies. As scavenger receptor class B, type I (SR-BI), the gene product of Scarb1, is known to regulate HDL metabolism, we recently characterized bone metabolism in Scarb1-null mice. These mice display high femoral bone mass associated with enhanced bone formation. As gender differences have been reported in HDL metabolism and SR-BI function, we investigated gender-specific bone alterations in Scarb1-null mice by microtomography and histology. We found 16% greater relative bone volume and 39% higher bone formation rate in the vertebrae from 2-month-old Scarb1-null females. No such alteration was seen in males, indicating gender- and region-specific differences in skeletal phenotype. Total and HDL-associated cholesterol levels, as well as ACTH plasma levels, were increased in both Scarb1-null genders, the latter being concurrent to impaired corticosterone response to fasting. Plasma levels of estradiol did not differ between null and WT females, suggesting that the estrogen metabolism alteration is not relevant to the higher vertebral bone mass in female Scarb1-null mice. Constitutively, high plasma levels of leptin along with 2.5-fold increase in its expression in white adipose tissue were measured in female Scarb1-null mice only. In vitro exposure of bone marrow stromal cells to ACTH and leptin promoted osteoblast differentiation as evidenced by increased gene expression of osterix and collagen type I alpha. Our results suggest that hyperleptinemia may account for the gender-specific high bone mass seen in the vertebrae of female Scarb1-null mice.
authors.affiliation: Laboratoire du Métabolisme OsseuxBioMed, Département des Sciences Biologiques Université du Québec à Montréal, Case Postale 8888, Succursale Centre-ville, Montréal, Quebec, Canada H3C 3P8Laboratoire du Métabolisme des LipoprotéinesBioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada H3C 3P8.
authors.forename: Corine
authors.initials: C
authors.lastname: Martineau
authors.affiliation: Laboratoire du Métabolisme OsseuxBioMed, Département des Sciences Biologiques Université du Québec à Montréal, Case Postale 8888, Succursale Centre-ville, Montréal, Quebec, Canada H3C 3P8Laboratoire du Métabolisme des LipoprotéinesBioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada H3C 3P8.
authors.forename: Louise
authors.initials: L
authors.lastname: Martin-Falstrault
authors.affiliation: Laboratoire du Métabolisme OsseuxBioMed, Département des Sciences Biologiques Université du Québec à Montréal, Case Postale 8888, Succursale Centre-ville, Montréal, Quebec, Canada H3C 3P8Laboratoire du Métabolisme des LipoprotéinesBioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada H3C 3P8.
authors.forename: Louise
authors.initials: L
authors.lastname: Brissette
authors.affiliation: Laboratoire du Métabolisme OsseuxBioMed, Département des Sciences Biologiques Université du Québec à Montréal, Case Postale 8888, Succursale Centre-ville, Montréal, Quebec, Canada H3C 3P8Laboratoire du Métabolisme des LipoprotéinesBioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada H3C 3P8 moreau.robert@uqam.ca.
authors.forename: Robert
authors.initials: R
authors.lastname: Moreau
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000494:pharmacology; D000818:Animals; D015519:Bone Density; D002454:Cell Differentiation / Q000187:drug effects; D008076:Cholesterol, HDL / Q000378:metabolism; D024042:Collagen Type I / Q000096:biosynthesis; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D005269:Femur / Q000378:metabolism*; D020738:Leptin / Q000097:blood* / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis; D051122:Scavenger Receptors, Class B / Q000172:deficiency*; D012737:Sex Factors; D000076182:Sp7 Transcription Factor; D013131:Spine / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis; D055114:X-Ray Microtomography
chemical_list: D008076:Cholesterol, HDL; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D020738:Leptin; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D000324:Adrenocorticotropic Hormone
keywords: SR-BI; Scarb1; adrenocorticotropin; corticosterone; high bone mass; leptin; osteoblasts