title: CD73-generated adenosine promotes osteoblast differentiation.
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.
authors: Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors: Masahide
authors: M
authors: Takedachi
authors: Hiroyuki
authors: H
authors: Oohara
authors: Brenda J
authors: BJ
authors: Smith
authors: Mitsuyoshi
authors: M
authors: Iyama
authors: Mariko
authors: M
authors: Kobashi
authors: Kenichiro
authors: K
authors: Maeda
authors: Courtney L
authors: CL
authors: Long
authors: Mary B
authors: MB
authors: Humphrey
authors: Barbara J
authors: BJ
authors: Stoecker
authors: Satoru
authors: S
authors: Toyosawa
authors: Linda F
authors: LF
authors: Thompson
authors: Shinya
authors: S
authors: Murakami
mesh_terms: D016475:3T3 Cells; D015720:5'-Nucleotidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D005838:Genotype; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D010641:Phenotype; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D015398:Signal Transduction; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D055114:X-Ray Microtomography
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D015415:Biomarkers; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D015675:Osteocalcin; D015720:5'-Nucleotidase; D000241:Adenosine