On the Role of Subtype Selective Adenosine Receptor Agonists During Proliferation and Osteogenic Differentiation of Human Primary Bone Marrow Stromal Cells

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Costa, MA (Author) ICBAS; Barbosa, A (Author) Other; Neto, E (Author) Other; Sa e Sousa, A (Author) Other; Freitas, R (Author) Other; Neves, JM (Author) Other; Magalhaes Cardoso, T (Author) Other; Fátima Ferreirinha (Author) ICBAS; Paulo Correia de Sá (Author) ICBAS

Journal

Title: Journal of Cellular Physiology

Vol. 226

Pages: 1353-1366

ISSN: 0021-9541

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 79 Citations

Scopus - 81 Citations

Other information

Authenticus ID: P-002-S95

DOI: 10.1002/jcp.22458

Abstract (EN): Purines are important modulators of bone cell biology. ATP is metabolized into adenosine by human primary osteoblast cells (HPOC); due to very low activity of adenosine deaminase, the nucleoside is the end product of the ecto-nucleotidase cascade. We, therefore, investigated the expression and function of adenosine receptor subtypes (A(1), A(2A), A(2B), and A(3)) during proliferation and osteogenic differentiation of HPOC. Adenosine A(1) (CPA), A(2A) (CGS21680C), A(2B) (NECA), and A(3) (2-Cl-IB-MECA) receptor agonists concentration-dependently increased HPOC proliferation. Agonist-induced 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-Cl-IB-MECA was devoid of effect. Blockade of the A2B receptor with PSB603 prevented osteogenic differentiation by NECA. In the presence of the A(1) antagonist, DPCPX, CPA reduced ALP activity at 21 and 28 days in culture. At the same time points, blockade of A(2A) 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-specific receptors. The most abundant A(2B) receptor seems to have a consistent role in cell differentiation, which may be balanced through the relative strengths of A(1) or A(2A) receptors determining whether osteoblasts are driven into proliferation or differentiation. J. Cell. Physiol. 226: 1353-1366, 2011. (C) 2010 Wiley-Liss, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14