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.