CD73‐generated adenosine promotes osteoblast differentiation
- 31 August 2011
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 227 (6), 2622-2631
- https://doi.org/10.1002/jcp.23001
Abstract
CD731 is a GPI‐anchored cell surface protein with ecto‐5′‐nucleotidase enzyme activity that plays a crucial role in adenosine production. While the roles of adenosine receptors (AR) on osteoblasts and osteoclasts have been unveiled to some extent, the roles of CD73 and CD73‐generated adenosine in bone tissue are largely unknown. To address this issue, we first analyzed the bone phenotype of CD73‐deficient (cd73−/−) mice. The mutant male mice showed osteopenia, with significant decreases of osteoblastic markers. Levels of osteoclastic markers were, however, comparable to those of wild‐type mice. A series of in vitro studies revealed that CD73 deficiency resulted in impairment in osteoblast differentiation but not in the number of osteoblast progenitors. In addition, over expression of CD73 on MC3T3‐E1 cells resulted in enhanced osteoblastic differentiation. Moreover, MC3T3‐E1 cells expressed adenosine A2A receptors (A2AAR) and A2B receptors (A2BAR) and expression of these receptors increased with osteoblastic differentiation. Enhanced expression of osteocalcin (OC) and bone sialoprotein (BSP) observed in MC3T3‐E1 cells over expressing CD73 were suppressed by treatment with an A2BAR antagonist but not with an A2AAR antagonist. Collectively, our results indicate that CD73 generated adenosine positively regulates osteoblast differentiation via A2BAR signaling. J. Cell. Physiol. 227: 2622–2631, 2012.Keywords
This publication has 44 references indexed in Scilit:
- Adenosine A1receptors (A1Rs) play a critical role in osteoclast formation and functionThe FASEB Journal, 2010
- Adenosine A1 receptors regulate bone resorption in mice: Adenosine A1 receptor blockade or deletion increases bone density and prevents ovariectomy‐induced bone loss in adenosine A1 receptor–knockout miceArthritis & Rheumatism, 2010
- Expression, signaling, and function of P2X7 receptors in bonePurinergic Signalling, 2009
- Where Wnts Went: The Exploding Field of Lrp5 and Lrp6 Signaling in BoneJournal of Bone and Mineral Research, 2009
- Adenosine A2A receptors play an active role in mouse bone marrow-derived mesenchymal stem cell developmentJournal of Leukocyte Biology, 2008
- Adenosine receptors: therapeutic aspects for inflammatory and immune diseasesNature Reviews Drug Discovery, 2008
- Osteoblast expression of an engineered G s -coupled receptor dramatically increases bone massProceedings of the National Academy of Sciences of the United States of America, 2008
- Activation of the hypoxia-inducible factor-1α pathway accelerates bone regenerationProceedings of the National Academy of Sciences of the United States of America, 2008
- The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal developmentJCI Insight, 2007
- The Type I Collagen Fragments ICTP and CTX Reveal Distinct Enzymatic Pathways of Bone Collagen DegradationJournal of Bone and Mineral Research, 2003