Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-2-22
pubmed:abstractText
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 A(2B) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1097-4652
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
226
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1353-66
pubmed:meshHeading
pubmed-meshheading:20945394-Adenosine, pubmed-meshheading:20945394-Adenosine Monophosphate, pubmed-meshheading:20945394-Adenosine Triphosphate, pubmed-meshheading:20945394-Aged, pubmed-meshheading:20945394-Alkaline Phosphatase, pubmed-meshheading:20945394-Biological Markers, pubmed-meshheading:20945394-Bone Marrow Cells, pubmed-meshheading:20945394-Cell Differentiation, pubmed-meshheading:20945394-Cell Proliferation, pubmed-meshheading:20945394-Cells, Cultured, pubmed-meshheading:20945394-Chromatography, High Pressure Liquid, pubmed-meshheading:20945394-Dose-Response Relationship, Drug, pubmed-meshheading:20945394-Female, pubmed-meshheading:20945394-Humans, pubmed-meshheading:20945394-Immunohistochemistry, pubmed-meshheading:20945394-Middle Aged, pubmed-meshheading:20945394-Osteoblasts, pubmed-meshheading:20945394-Osteogenesis, pubmed-meshheading:20945394-Purinergic P1 Receptor Agonists, pubmed-meshheading:20945394-Purinergic P1 Receptor Antagonists, pubmed-meshheading:20945394-Receptors, Purinergic P1, pubmed-meshheading:20945394-Stromal Cells, pubmed-meshheading:20945394-Time Factors
pubmed:year
2011
pubmed:articleTitle
On the role of subtype selective adenosine receptor agonists during proliferation and osteogenic differentiation of human primary bone marrow stromal cells.
pubmed:affiliation
Laboratório de Farmacologia e Neurobiologia, UMIB, Instituto de Ciências Biomédicas Abel Salazar - Universidade do Porto (ICBAS-UP), Portugal.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't