title: Adenosine Triphosphate stimulates differentiation and mineralization in human osteoblast-like Saos-2 cells.
abstract: In the last years adenosine triphosphate (ATP) and subsequent purinergic system activation through P2 receptors were investigated highlighting their pivotal role in bone tissue biology. In osteoblasts ATP can regulate several activities like cell proliferation, cell death, cell differentiation and matrix mineralization. Since controversial results exist, in this study we analyzed the ATP effects on differentiation and mineralization in human osteoblast-like Saos-2 cells. We showed for the first time the altered functional activity of ATP receptors. Despite that, we found that ATP can reduce cell proliferation and stimulate osteogenic differentiation mainly in the early stages of in vitro maturation as evidenced by the enhanced expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2) and Osteocalcin (OC) genes and by the increased ALP activity. Moreover, we found that ATP can affect mineralization in a biphasic manner, at low concentrations ATP always increases mineral deposition while at high concentrations it always reduces mineral deposition. In conclusion, we show the osteogenic effect of ATP on both early and late stage activities like differentiation and mineralization, for the first time in human osteoblastic cells.
authors.affiliation: Department of Orthopaedics and Traumatology, University Hospital Foundation, Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy.|National Centre for Rare Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, 00161, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cutarelli
authors.affiliation: Department of Medicine of Systems, University of Rome Tor Vergata, Via Montpellier 1, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Marini
authors.affiliation: Department of Medicine of Systems, University of Rome Tor Vergata, Via Montpellier 1, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Tancredi
authors.affiliation: Department of Medicine of Systems, University of Rome Tor Vergata, Via Montpellier 1, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Arcangelo
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, Rome, 00133, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Murdocca
authors.affiliation: National Centre for Rare Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, 00161, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Frank
authors.affiliation: Department of Orthopaedics and Traumatology, University Hospital Foundation, Policlinico Tor Vergata, Viale Oxford 81, Rome, 00133, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Tarantino
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D002113:Calcification, Physiologic / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D015675:Osteocalcin; D000255:Adenosine Triphosphate; D000469:Alkaline Phosphatase
keywords: adenosine triphosphate; cell differentiation; minerals; osteoblasts; purinergic P2; receptors