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We, therefore, investigated the expression and function of adenosine receptor subtypes (A<jats:sub>1<\/jats:sub>, A<jats:sub>2A<\/jats:sub>, A<jats:sub>2B<\/jats:sub>, and A<jats:sub>3<\/jats:sub>) during proliferation and osteogenic differentiation of HPOC. Adenosine A<jats:sub>1<\/jats:sub>(CPA), A<jats:sub>2A<\/jats:sub>(CGS21680C), A<jats:sub>2B<\/jats:sub>(NECA), and A<jats:sub>3<\/jats:sub>(2\u2010Cl\u2010IB\u2010MECA) receptor agonists concentration\u2010dependently increased HPOC proliferation. Agonist\u2010induced HPOC proliferation was prevented by their selective antagonists, DPCPX, SCH442416, PSB603, and MRS1191. CPA and NECA facilitated osteogenic differentiation measured by increases in alkaline phosphatase (ALP) activity. This contrasts with the effect of CGS21680C which delayed HPOC differentiation; 2\u2010Cl\u2010IB\u2010MECA was devoid of effect. Blockade of the A<jats:sub>2B<\/jats:sub>receptor with PSB603 prevented osteogenic differentiation by NECA. In the presence of the A<jats:sub>1<\/jats:sub>antagonist, DPCPX, CPA reduced ALP activity at 21 and 28 days in culture. At the same time points, blockade of A<jats:sub>2A<\/jats:sub>receptors with SCH442416 transformed the inhibitory effect of CGS21680C into facilitation. Inhibition of adenosine uptake with dipyridamole caused a net increase in osteogenic differentiation. The presence of all subtypes of adenosine receptors on HPOC was confirmed by immunocytochemistry. Data show that adenosine is an important regulator of osteogenic cell differentiation through the activation of subtype\u2010specific receptors. The most abundant A<jats:sub>2B<\/jats:sub>receptor seems to have a consistent role in cell differentiation, which may be balanced through the relative strengths of A<jats:sub>1<\/jats:sub>or A<jats:sub>2A<\/jats:sub>receptors determining whether osteoblasts are driven into proliferation or differentiation. J. Cell. Physiol. 226: 1353\u20131366, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22458","type":"journal-article","created":{"date-parts":[[2010,10,13]],"date-time":"2010-10-13T14:20:22Z","timestamp":1286979622000},"page":"1353-1366","source":"Crossref","is-referenced-by-count":109,"title":["On the role of subtype selective adenosine receptor agonists during proliferation and osteogenic differentiation of human primary bone marrow stromal cells"],"prefix":"10.1002","volume":"226","author":[{"given":"M. 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