title: The effect of class a scavenger receptor deficiency in bone.
abstract: Class A scavenger receptor (SR-A) is predominantly expressed by macrophages, and because osteoclasts are of monocyte/macrophage lineage, SR-A is of potential interest in osteoclast biology. In addition to modified low density lipoprotein uptake, SR-A is also important in cell attachment and signaling. In this study we evaluated the effect of SR-A deletion on bone. Knock-out animals have 40% greater body weight than wild type. Body composition analyses demonstrated that total lean and fat body mass were greater in knock-out animals, but there was no significant difference in percent fat and lean body mass. Bone mineral density and content were significantly greater in knock-out compared with wild type animals. Micro-computed tomography analyses confirmed that total volume, bone volume as well as trabecular number, thickness, and connectivity were significantly greater in knock-out mice. As expected, trabecular separation was greater in wild type mice. The phenotype appears to be explained by 60% fewer osteoclasts in females and 35% fewer in males compared to wild type mice with a paradoxical increase in nuclei/osteoclast in knock-out animals. Furthermore, there were no differences in adipocyte number and osteoblast number or activity. The addition of the soluble extracellular domain of SR-A to RAW264.7 cells stimulated a concentration-dependent increase in osteoclast differentiation that was receptor activator of nuclear factor-kappaB ligand (RANKL)-dependent. Soluble SR-A had no effect on cell proliferation in the presence of RANKL but stimulated a 40% increase in numbers in the absence of RANKL. We conclude that SR-A plays a role in normal osteoclast differentiation, suggesting a novel role for this receptor in bone biology.
authors.affiliation: College of Dentistry, Department of Internal Medicine, Divisions of University of Kentucky, Lexington, Kentucky 40536.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Digestive Diseases and Nutrition and University of Kentucky, Lexington, Kentucky 40536; Lexington Veterans Affairs Medical Center, Lexington, Kentucky 40502.
authors.forename: Willem J S
authors.initials: WJS
authors.lastname: de Villiers
authors.affiliation: Lexington Veterans Affairs Medical Center, Lexington, Kentucky 40502; Microbiology, Immunology and Molecular Genetics and University of Kentucky, Lexington, Kentucky 40536.
authors.forename: Beth
authors.initials: B
authors.lastname: Garvy
authors.affiliation: Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky 40536.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Post
authors.affiliation: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294, and.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Nagy
authors.affiliation: Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
authors.forename: Fayez F
authors.initials: FF
authors.lastname: Safadi
authors.affiliation: Nephrology, Bone, and Mineral Metabolism, and Departments of University of Kentucky, Lexington, Kentucky 40536.
authors.forename: Marie Claude
authors.initials: MC
authors.lastname: Faugere
authors.affiliation: Nephrology, Bone, and Mineral Metabolism, and Departments of University of Kentucky, Lexington, Kentucky 40536.
authors.forename: Guodong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Nephrology, Bone, and Mineral Metabolism, and Departments of University of Kentucky, Lexington, Kentucky 40536.
authors.forename: Hartmut H
authors.initials: HH
authors.lastname: Malluche
authors.affiliation: Lexington Veterans Affairs Medical Center, Lexington, Kentucky 40502; Nephrology, Bone, and Mineral Metabolism, and Departments of University of Kentucky, Lexington, Kentucky 40536. Electronic address: JohnWilliams@uky.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Williams
mesh_terms: D000818:Animals; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D015519:Bone Density / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D005269:Femur / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D017434:Protein Structure, Tertiary; D053245:RANK Ligand / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000172:deficiency* / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D053245:RANK Ligand; D051117:Scavenger Receptors, Class A; C505689:Tnfsf11 protein, mouse