RRC ID 43572
Author Takedachi M, Oohara H, Smith BJ, Iyama M, Kobashi M, Maeda K, Long CL, Humphrey MB, Stoecker BJ, Toyosawa S, Thompson LF, Murakami S.
Title CD73-generated adenosine promotes osteoblast differentiation.
Journal J Cell Physiol
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.
Volume 227(6)
Pages 2622-31
Published 2012-6-1
DOI 10.1002/jcp.23001
PMID 21882189
PMC PMC3237726
MeSH 3T3 Cells 5'-Nucleotidase / deficiency 5'-Nucleotidase / genetics 5'-Nucleotidase / metabolism* Adenosine / metabolism* Adenosine A2 Receptor Antagonists / pharmacology Animals Biomarkers / metabolism Bone Diseases, Metabolic / diagnostic imaging Bone Diseases, Metabolic / enzymology Bone Diseases, Metabolic / genetics Bone Diseases, Metabolic / pathology Cell Differentiation* / drug effects Femur / diagnostic imaging Femur / drug effects Femur / enzymology* Femur / pathology Genotype Humans Integrin-Binding Sialoprotein / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Osteoblasts / drug effects Osteoblasts / enzymology* Osteoblasts / pathology Osteocalcin / metabolism Osteogenesis Phenotype Receptor, Adenosine A2A / metabolism Receptor, Adenosine A2B / metabolism Signal Transduction Tibia / diagnostic imaging Tibia / drug effects Tibia / enzymology* Tibia / pathology Time Factors Transfection X-Ray Microtomography
IF 5.546
Times Cited 64
Human and Animal Cells MC3T3-E1(RCB1126)