Adenosine receptor subtype expression and activation influence the differentiation of mesenchymal stem cells to osteoblasts and adipocytes

Gharibi, Borzo, Abraham, Anju Ann, Ham, Jack and Evans, Bronwen Alice James ORCID: https://orcid.org/0000-0002-3082-1008 2011. Adenosine receptor subtype expression and activation influence the differentiation of mesenchymal stem cells to osteoblasts and adipocytes. Journal of Bone and Mineral Research 26 (9) , pp. 2112-2124. 10.1002/jbmr.424

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Abstract

Osteoblasts and adipocytes differentiate from a common precursor cell, the mesenchymal stem cell (MSC). Adenosine is known to signal via four adenosine receptor subtypes, and significantly, recent findings indicate that these may play a role in MSC differentiation. We therefore investigated adenosine receptor expression and activation during the differentiation of MSCs to osteoblasts and adipocytes. The A2BR was dominant in MSCs, and its expression and activity were transiently upregulated at early stages of osteoblastic differentiation. Both activation and overexpression of A2BR induced the expression of osteoblast-related genes [Runx2 and alkaline phosphatase (ALP)], as well as ALP activity, and stimulation increased osteoblast mineralization. The expression of A2AR was upregulated during later stages of osteoblastic differentiation, when its activation stimulated ALP activity. Differentiation of MSCs to adipocytes was accompanied by significant increases in A1R and A2AR expression, and their activation was associated with increased adipogenesis. Enhanced A2AR expression was sufficient to promote expression of adipocyte-related genes (PPAR and C/EBP), and its activation resulted in increased adipocytic differentiation and lipid accumulation. In contrast, the A1R was involved mainly in lipogenic activity of adipocytes rather than in their differentiation. These results show that adenosine receptors are differentially expressed and involved in lineage-specific differentiation of MSCs. We conclude, therefore, that fruitful strategies for treating diseases associated with an imbalance in the differentiation and function of these lineages should include targeting adenosine receptor signal pathways. Specifically, these research avenues will be useful in preventing or treating conditions with insufficient bone or excessive adipocyte formation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
Uncontrolled Keywords:	Adensoine receptor; Osteoblast; Adipocyte; Mesenchymal stem cell; Differentiation
Publisher:	Wiley Blackwell
ISSN:	0884-0431
Date of First Compliant Deposit:	30 March 2016
Last Modified:	09 May 2023 17:43
URI:	https://orca.cardiff.ac.uk/id/eprint/22874

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