The effect of class a scavenger receptor deficiency in bone.
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.
Lin
Yi-Ling
YL
College of Dentistry, Department of Internal Medicine, Divisions of University of Kentucky, Lexington, Kentucky 40536.
de Villiers
Willem J S
WJS
Digestive Diseases and Nutrition and University of Kentucky, Lexington, Kentucky 40536; Lexington Veterans Affairs Medical Center, Lexington, Kentucky 40502.
Garvy
Beth
B
Lexington Veterans Affairs Medical Center, Lexington, Kentucky 40502; Microbiology, Immunology and Molecular Genetics and University of Kentucky, Lexington, Kentucky 40536.
Post
Steven R
SR
Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, Kentucky 40536.
Nagy
Tim R
TR
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294, and.
Safadi
Fayez F
FF
Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Faugere
Marie Claude
MC
Nephrology, Bone, and Mineral Metabolism, and Departments of University of Kentucky, Lexington, Kentucky 40536.
Wang
Guodong
G
Nephrology, Bone, and Mineral Metabolism, and Departments of University of Kentucky, Lexington, Kentucky 40536.
Malluche
Hartmut H
HH
Nephrology, Bone, and Mineral Metabolism, and Departments of University of Kentucky, Lexington, Kentucky 40536.
Williams
John P
JP
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.
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*
D053245:RANK Ligand; D051117:Scavenger Receptors, Class A; C505689:Tnfsf11 protein, mouse