title: The atherogenic Scarb1 null mouse model shows a high bone mass phenotype.
abstract: Scavenger receptor class B, type I (SR-BI), the Scarb1 gene product, is a receptor associated with cholesteryl ester uptake from high-density lipoproteins (HDL), which drives cholesterol movement from peripheral tissues toward the liver for excretion, and, consequently, Scarb1 null mice are prone to atherosclerosis. Because studies have linked atherosclerosis incidence with osteoporosis, we characterized the bone metabolism in these mice. Bone morphometry was assessed through microcomputed tomography and histology. Marrow stromal cells (MSCs) were used to characterize influence of endogenous SR-BI in cell functions. Total and HDL-associated cholesterol in null mice were increased by 32-60%, correlating with its role in lipoprotein metabolism. Distal metaphyses from 2- and 4-mo-old null mice showed correspondingly 46 and 37% higher bone volume fraction associated with a higher number of trabeculae. Histomorphometric analyses in 2-mo-old null male mice revealed 1.42-fold greater osteoblast surface, 1.37-fold higher percent mineralizing surface, and 1.69-fold enhanced bone formation rate. In vitro assays for MSCs from null mice revealed 37% higher proliferation rate, 48% more alkaline phosphatase activity, 70% greater mineralization potential and a 2-fold osterix (Sp7) expression, yet a 0.5-fold decrease in caveolin-1 (Cav1) expression. Selective uptake levels of HDL-associated cholesteryl oleate and estradiol were similar between MSC from wild-type and Scarb1 null mice, suggesting that its contribution to this process is not its main role in these cells. However, Scarb1 knockout stunted the HDL-dependent regulation of Cav1 genic expression. Scarb1 null mice are not prone to osteoporosis but show higher bone mass associated with enhanced bone formation.
authors.affiliation: Laboratoire du Métabolisme Osseux, BioMed, Université du Québec à Montréal, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada; and.
authors.forename: Corine
authors.initials: C
authors.lastname: Martineau
authors.forename: Louise
authors.initials: L
authors.lastname: Martin-Falstrault
authors.forename: Louise
authors.initials: L
authors.lastname: Brissette
authors.forename: Robert
authors.initials: R
authors.lastname: Moreau
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000150:complications* / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002113:Calcification, Physiologic; D051242:Caveolin 1 / Q000235:genetics; D049109:Cell Proliferation; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000473:pathology; D010012:Osteogenesis; D010024:Osteoporosis / Q000209:etiology*; D051122:Scavenger Receptors, Class B / Q000172:deficiency* / Q000502:physiology*; D017154:Stromal Cells / Q000473:pathology
chemical_list: D051242:Caveolin 1; D008076:Cholesterol, HDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol
keywords: adrenocorticotropic hormone; caveolin-1; high-density lipoprotein; osteoblasts