title: Role of the P2Y13 receptor in the differentiation of bone marrow stromal cells into osteoblasts and adipocytes.
abstract: 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. P2Y13 -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 P2Y13 R activation was involved in the osteogenic differentiation of MSC. Our study demonstrated that ADP stimulation of P2Y13 R(+/+) (but not P2Y13 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 P2Y13 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 P2Y13 R(-/-) BMSCs were incubated in an adipogenic medium, the number of adipocytes generated and the level of adipogenic gene expression (PPARγ2 and Adipsin) were higher than those obtained in P2Y13 R(+/+) MSC. Interestingly, we observed a significant increase of the number of bone marrow adipocytes in tibia of P2Y13 R(-/-) mice. In conclusion, our findings indicate that the P2Y13 R plays an important role in the balance of osteoblast and adipocyte terminal differentiation of bone marrow progenitors. Therefore, the P2Y13 receptor can be considered as a new pharmacological target for the treatment of bone diseases like osteoporosis. STEM Cells 2013;31:2747-2758.
authors: Institute of Interdisciplinary Research, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium.
authors: Galadrielle
authors: G
authors: Biver
authors: Ning
authors: N
authors: Wang
authors: Alison
authors: A
authors: Gartland
authors: Isabel
authors: I
authors: Orriss
authors: Timothy R
authors: TR
authors: Arnett
authors: Jean-Marie
authors: JM
authors: Boeynaems
authors: Bernard
authors: B
authors: Robaye
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C486689:P2ry13 protein, mouse; D018048:Receptors, Purinergic P2
keywords: Adipocyte; Differentiation; Knockout mice; Mesenchymal stem cell; Osteoblast; P2Y13 receptor