A role for the immunomodulatory molecules CD200 and CD200R in regulating bone formation.
Altered osteoprotogerin (OPG) and OPG ligand (RANKL) ratios are known to regulate bone metabolism. We investigated whether CD200:CD200R interaction would alter OPG:RANKL ratios, and thus modulate bone differentiation in cultures derived from neonatal calvariae, a source of osteoblast precursors (OBp), or bone marrow-derived myeloid cells as a source of osteoclast precursors (OCp). We characterized cells in cultures using real-time PCR to measure expression of a number of mRNAs characteristic of cells differentiating towards the osteoblast or osteoclast lineage, and enumerated bone nodule formation and osteoclasts directly. CD200Fc or anti-CD200 mAbs were included as modulating agents. In addition, calvariae from transgenic mice overexpressing CD200 under control of a doxycycline-inducible promoter were used as a source of OBp endogenously overexpressing CD200. Our data show that increased endogenous expression of CD200 on OBp, or addition of CD200Fc into cultures, led to increased OPG:RANKL ratios and increased bone nodule growth, while anti-CD200 abolished this effect.
Lee
L
L
The Toronto Hospital, University Health Network, Toronto, Canada.
Liu
J
J
Manuel
J
J
Gorczynski
R M
RM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; C492346:CD200 receptor, mouse; D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; C042739:antigens, CD200