Biver, G., Wang, N., Gartland, A. orcid.org/0000-0002-3712-2437 et al. (4 more authors) (2013) Role of the P2Y(13) Receptor in the Differentiation of Bone Marrow Stromal Cells into Osteoblasts and Adipocytes. STEM CELLS, 31 (12). pp. 2747-2758. ISSN 1066-5099
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 P2Y13R activation was involved in the osteogenic differentiation of MSC. Our study demonstrated that ADP stimulation of P2Y13R+/+ (but not P2Y13R-/-) 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 P2Y13R-/- 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 P2Y13R-/- 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 P2Y13R+/+ MSC. Interestingly, we observed a significant increase of the number of bone marrow adipocytes in tibia of P2Y13R-/- mice. In conclusion, our findings indicate that the P2Y13R 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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2013 AlphaMed Press. This is an author produced version of a paper subsequently published in STEM CELLS. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | P2Y(13) receptor; Knockout mice; Mesenchymal stem cell; Osteoblast; Adipocyte; Differentiation |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 Apr 2016 15:09 |
Last Modified: | 25 Mar 2018 15:18 |
Published Version: | http://dx.doi.org/10.1002/stem.1411 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/stem.1411 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:97679 |