The CD200/CD200R axis: new control mechanism of bone remodeling

      Bone is a highly dynamic tissue that is constantly remodeled by a process involving bone resorption by osteoclasts and bone formation by osteoblasts. An intricate balance between the activities of these two cell types maintains bone’s physiology. We identified CD200 and CD200R as new players in bone remodeling controlling osteoblast differentiation as well as osteoclast formation. CD200 is an immunoglobulin superfamilly member expressed on various cell types including mesenchymal stem cells (MSCs). We observed that only a subpopulation of cultured MSCs was positive for the CD200. The CD200 positive MSCs over expressed α−smooth muscle actin and several osteoblastic markers compared to CD200 negative MSCs and were more likely to mineralize extra-cellular matrix. In addition, osteogenic differentiation using BMP4 strongly induced CD200 expression. Similarly, pro-inflammatory cytokines IL-1β and TNFα increased CD200 expression at MSC membrane but inhibited osteoblastic commitment. These data show that CD200 is involved during osteoblastic commitment of MSCs. Interestingly, we demonstrated that CD200 also controlled osteoclast formation. In vitro, soluble CD200 inhibited differentiation as well as maturation of CD200R-positive osteoclast precursors into bone-resorbing cells. Soluble CD200 did not modify the monocyte phenotype but inhibited the RANKL signaling pathway as well as the expression of mature osteoclast markers. Finally, we found that MSCs inhibited osteoclast formation and this inhibition was related to CD200 expression on the MSC surface. These results clearly demonstrate that MSCs play a major role in the regulation of bone resorption. Altogether our data demonstrate that the CD200-CD200R couple plays a critical role in bone remodeling and could be a new target to control bone diseases.
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