Transdifferentiation of human and mouse osteoblasts to adipocytes is accompanied with changes in adenosine receptor expression [Abstract]

Gharibi, B., Ham, Jack and Evans, B. A. J. 2010. Transdifferentiation of human and mouse osteoblasts to adipocytes is accompanied with changes in adenosine receptor expression [Abstract]. Purinergic Signalling 6 (1) , pp. 125-144. 10.1007/s11302-009-9175-x

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Abstract

Trans-differentiation of osteoblasts into adipocytes plays a role in the development of diseases such as osteoporosis. We have investigated adenosine receptor (AR) signalling and function in a) the 7F2 mouse osteoblast cell line and b) human primary osteoblasts (HOB), as they differentiate into adipocytes. AR expression during differentiation was determined by qRT-PCR, western analysis and cAMP studies. The effects of AR agonists on osteoblast (alkaline phosphatase, osteocalcin, mineralisation) and adipocyte (PPARγ, lipoprotein lipase (LPL) and Oil Red O/Nile Red staining) markers were also determined. Trans-differentiation of 7F2 cells to adipocytes was accompanied with an increase in expression of A1R (>1800-fold; P < 0.0001) and reductions in A2aR and A2bR mRNA (respectively 80% and 78%; P < 0.0001). AR protein expression changes paralleled those for mRNA and was in keeping with changes in cAMP responses to NECA which were down-regulated by 70% (P < 0.01) in 7F2 adipocytes when compared with undifferentiated cells. In contrast, HOB differentiated adipocytes showed a significant reduction in A1R mRNA (90%, P < 0.0001) but no change in the other receptors. Trans-differentiation of both 7F2 and HOB cells to adipocytes was demonstrated by increased lipid and expression of PPARλ and LPL (P < 0.0001) but reduced expression of osteocalcin (P < 0.0001). The stable AR agonist, NECA reduced ALP and osteocalcin in undifferentiated 7F2 and HOB cells after 5–7 days of exposure, (in HOB cells the reductions in marker expression were 30%, P < 0.001). NECA also stimulated a 5-fold (P < 0.01) increase in LPL mRNA expression in HOB cells and induced adipogenesis in 7F2 cells (Oil Red O staining (P < 0.0001) and Nile Red FACS analysis (P < 0.0001). Although there were subtle differences in changes in AR expression as 7F2 and HOB cells differentiate to adipocytes; our data suggests that the A1R is associated with an adipocyte phenotype whereas the A2bR is more likely to be associated with an osteoblast phenotype.

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/30461

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