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CD73‐generated adenosine promotes osteoblast differentiation
Author(s) -
Takedachi Masahide,
Oohara Hiroyuki,
Smith Brenda J.,
Iyama Mitsuyoshi,
Kobashi Mariko,
Maeda Kenichiro,
Long Courtney L.,
Humphrey Mary B.,
Stoecker Barbara J.,
Toyosawa Satoru,
Thompson Linda F.,
Murakami Shinya
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.23001
Subject(s) - osteoblast , adenosine , osteocalcin , adenosine receptor , microbiology and biotechnology , chemistry , medicine , endocrinology , receptor , bone sialoprotein , cellular differentiation , alkaline phosphatase , biology , in vitro , biochemistry , enzyme , gene , agonist
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 A 2A receptors (A 2A AR) and A 2B receptors (A 2B AR) 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 A 2B AR antagonist but not with an A 2A AR antagonist. Collectively, our results indicate that CD73 generated adenosine positively regulates osteoblast differentiation via A 2B AR signaling. J. Cell. Physiol. 227: 2622–2631, 2012. © 2011 Wiley Periodicals, Inc.