Mesenchymal stem cell differentiation to osteoblasts is accompanied with increases in adenosine A2 receptor expression [Abstract]

Gharibi, B., Ham, Jack and Evans, B. A. J. 2010. Mesenchymal stem cell differentiation to osteoblasts is accompanied with increases in adenosine A2 receptor expression [Abstract]. Purinergic Signalling 6 (1) , pp. 125-144. 10.1007/s11302-009-9175-x

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Abstract

Adenosine mediates a variety of physiological functions by interacting with four cell surface G protein-coupled receptors: A1, A2a, A2b and A3. The aim of this study was to investigate adenosine receptor (AR) expression and function in mesenchymal stem cells (MSC) and as they differentiate into osteoblasts. MSC derived from rat femurs and tibias were differentiated into osteoblasts using dexamethasone and ascorbate-2-phosphate; β-glycerophosphate was added to induce calcium deposition (mineralisation). AR and osteoblast marker expression was assessed by a combination of qRT-PCR and Western blotting analysis, and cAMP levels were determined by radioimmunoassay. In undifferentiated MSCs, adenosine and NECA (stable universal AR agonist) stimulated the cAMP production by 10- and 24- (P < 0.0001) fold. NECA also stimulated alkaline phosphatase (ALP) mRNA expression and enzyme activity by 6- and 2-fold (P < 0.0001) respectively. Adenosine and NECA stimulated cAMP levels were increased respectively to 153- (P < 0.001) and 275-fold (P < 0.001) after 9 days of differentiation to osteoblasts. These data are consistent with the observed increases in A2aR and A2bR mRNA (8-fold; P < 0.0001 and 2-fold; P < 0.001) and protein (4-fold and 1.8-fold P < 0.05) expression. NECA also enhanced the expression of Cbfa1 from 4- to 7-fold (P < 0.01), ALP from 12- to 27-fold (P < 0.001) and ALP enzyme activity by up to 70% (P < 0.001) during osteoblastic differentiation. The stimulatory effects of NECA on ALP were inhibited in the presence of the A2bAR antagonist, MRS1706 (P < 0.001) and partly reversed by the A2aAR antagonist, SCH442416. NECA (10 days of exposure) also stimulated mineralisation up to 300%, (P < 0.003), an effect that was reversed with MRS1706. These data show that A2AR expression increases as MSC differentiate to osteoblasts, and that activation of these receptors is important for osteoblastogenesis and mineralisation. Targeting adenosine receptor signal pathways may thus be therapeutically useful for preventing or treating conditions where there is insufficient bone formation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Additional Information:	1st UK Purine Symposium, Sheffield, UK, 19th November 2009
Publisher:	Springer Verlag
ISSN:	1573-9538
Last Modified:	19 Mar 2016 22:53
URI:	https://orca.cardiff.ac.uk/id/eprint/30464

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