Extracellular calcium stimulates osteogenic differentiation of human adipose-derived stem cells by enhancing bone morphogenetic protein-2 expression

Risa Yanai, Fumi Tetsuo, Shinichi Ito, Momoe Itsumi, Junko Yoshizumi, Tomoko Maki, Yoshihide Mori, Yasutaka Kubota, Shunichi Kajioka

Research output: Contribution to journalArticle

Abstract

Bone morphogenetic protein-2 (BMP-2) promotes the differentiation of non-osteogenic mesenchymal cells to osteogenic cells. In this study, we isolated human adipose-derived stem cells (hASCs) and investigated the effects of recombinant human BMP-2 (rhBMP-2) and extracellular Ca2+ concentration ([Ca2+]out) on the osteogenic differentiation of hASCs. rhBMP-2 promoted calcium deposition in hASCs and stimulated the mRNA expressions of six proteins known to be involved in the osteogenic differentiation of hASCs: Runx2, osterix, alkaline phosphatase, osteonectin, bone sialoprotein and osteocalcin. Elevation of [Ca2+]out enhanced the level of alkaline phosphatase enzyme, increased the mRNA expressions of Runx2 and osteocalcin and induced the expressions of BMP-2 mRNA and protein in hASCs. Elevation of [Ca2+]out transiently increased the intracellular Ca2+ concentration ([Ca2+]in) due to activation of the calcium-sensing receptor (CaSR). The Ca2+-induced expressions of BMP-2 mRNA and protein were inhibited by the calmodulin antagonist, W-7. Furthermore, elevation of [Ca2+]out decreased the cytoplasmic level of phosphorylated nuclear factor of activated T-cell-2 (NFAT-2) and increased the nuclear level of dephosphorylated NFAT2. Taken together, these results suggest that rhBMP-2 promotes the osteogenic differentiation of hASCs. Furthermore, an increase in [Ca2+]out enhances the expression of BMP-2 via activation of the CaSR, elevation of [Ca2+]in and stimulation of Ca2+/calmodulin-dependent NFAT-signaling pathways.

Original languageEnglish
Article number102058
JournalCell Calcium
Volume83
DOIs
Publication statusPublished - Nov 2019

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Bone Morphogenetic Protein 2
Stem Cells
Calcium
Calcium-Sensing Receptors
Messenger RNA
Osteocalcin
Calmodulin
Alkaline Phosphatase
Osteonectin
Integrin-Binding Sialoprotein
NFATC Transcription Factors
Proteins
Enzymes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

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Extracellular calcium stimulates osteogenic differentiation of human adipose-derived stem cells by enhancing bone morphogenetic protein-2 expression. / Yanai, Risa; Tetsuo, Fumi; Ito, Shinichi; Itsumi, Momoe; Yoshizumi, Junko; Maki, Tomoko; Mori, Yoshihide; Kubota, Yasutaka; Kajioka, Shunichi.

In: Cell Calcium, Vol. 83, 102058, 11.2019.

Research output: Contribution to journalArticle

Yanai, Risa ; Tetsuo, Fumi ; Ito, Shinichi ; Itsumi, Momoe ; Yoshizumi, Junko ; Maki, Tomoko ; Mori, Yoshihide ; Kubota, Yasutaka ; Kajioka, Shunichi. / Extracellular calcium stimulates osteogenic differentiation of human adipose-derived stem cells by enhancing bone morphogenetic protein-2 expression. In: Cell Calcium. 2019 ; Vol. 83.
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