Role of the P2Y13 Receptor in the Differentiation of Bone Marrow Stromal Cells into Osteoblasts and Adipocytes

Accumulating evidence indicates that extracellular nucleotides, signaling through purinergic receptors, play a significant role in bone remodeling. Mesenchymal stem cells (MSCs) express functional P2Y receptors whose expression level is regulated during osteoblast or adipocyte differentiation. P2Y(13)-deficient mice were previously shown to exhibit a decreased bone turnover associated with a reduction in the number of both osteoblasts and osteoclasts on the bone surfaces. We therefore examined whether P2Y(13)R activation was involved in the osteogenic differentiation of MSC. Our study demonstrated that ADP stimulation of P2Y(13)R(+/+) (but not P2Y(13)R(-/-)) adherent bone marrow stromal cells (BMSCs) increased significantly the formation of alkaline phosphatase-colony-forming units (CFU-ALP) as well as the expression of osteoblastic markers (osterix, alkaline phosphatase, and collagen I) involved in the maturation of preosteoblasts into osteoblasts. The number of CFU-ALP obtained from P2Y(13)R(-/-) BMSC and the level of osteoblastic gene expression after osteogenic stimulation were strongly reduced compared to those obtained in wild-type cell cultures. In contrast, when P2Y(13)R(-/-) BMSCs were incubated in an adipogenic medium, the number of adipocytes generated and the level of adipogenic gene expression (PPAR2 and Adipsin) were higher than those obtained in P2Y(13)R(+/+) MSC. Interestingly, we observed a significant increase of the number of bone marrow adipocytes in tibia of P2Y(13)R(-/-) mice. In conclusion, our findings indicate that the P2Y(13)R plays an important role in the balance of osteoblast and adipocyte terminal differentiation of bone marrow progenitors. Therefore, the P2Y(13) receptor can be considered as a new pharmacological target for the treatment of bone diseases like osteoporosis.