Adenosine Triphosphate stimulates differentiation and mineralization in human osteoblast-like Saos-2 cells

Dev Growth Differ. 2016 May;58(4):400-8. doi: 10.1111/dgd.12288. Epub 2016 May 18.

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.

Keywords: adenosine triphosphate; cell differentiation; minerals; osteoblasts; purinergic P2; receptors.

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Alkaline Phosphatase / biosynthesis
  • Calcification, Physiologic / drug effects*
  • Cell Differentiation / drug effects*
  • Cell Line
  • Core Binding Factor Alpha 1 Subunit / biosynthesis
  • Gene Expression Regulation / drug effects
  • Humans
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteocalcin / biosynthesis

Substances

  • Core Binding Factor Alpha 1 Subunit
  • RUNX2 protein, human
  • Osteocalcin
  • Adenosine Triphosphate
  • Alkaline Phosphatase