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

• Published in: Cell calcium (Edinburgh) Vol. 83; p. 102058
• Main Authors: Yanai, Risa, Tetsuo, Fumi, Ito, Shinichi, Itsumi, Momoe, Yoshizumi, Junko, Maki, Tomoko, Mori, Yoshihide, Kubota, Yasutaka, Kajioka, Shunichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2019
• Subjects: BMP-2; Extracellular Ca2; Human adipose-derived stem cells; Osteogenic; Human adipose-derived stem cells; Extracellular Ca2; Osteogenic; BMP-2; Extracellular Ca(2+)
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2019.102058

[Display omitted] 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.