Crosstalk between tyrosine kinase receptors, GSK3 and BMP2 signaling during osteoblastic differentiation of human mesenchymal stem cells

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• 作者：Emmanuel Biver ; Cyril Thouverey ; David Magne ; Joseph Caverzasio
• 关键词：BMPs ; bone morphogenic proteins ; TGF-尾 ; transforming growth factor beta ; MSC ; mesenchymal stem cell ; PDGF ; platelet derived growth factor ; FGF ; fibroblast growth factor ; EGF ; epidermal growth factor ; RTK ; receptors tyrosine kinase ; HMSC ; human MSC ; ALP ; alkaline phosphatase ; MAPK ; Mitogen-Activated-Protein Kinase ; ERK ; extracellular signal regulated kinases ; JNK ; c-Jun amino-terminal kinases ; GSK3 ; glycogen synthase kinase 3 ; OSX ; osterix ; BSP ; bone sialoprotein
• 刊名：Molecular and Cellular Endocrinology
• 出版年：25 January, 2014
• 年：2014
• 卷：382
• 期：1
• 页码：120-130
• 全文大小：1471 K

文摘

Bone morphogenic proteins (BMPs) promote mesenchymal stem cell (MSC) osteogenic differentiation, whereas platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) activate their proliferation through receptors tyrosine kinase (RTK). The effects of PDGF or FGF receptor signaling pathway on BMP2-induced osteoblastic differentiation was investigated in human MSC (HMSC). Inhibition of PDGF or/and FGF receptors enhanced BMP2-induced alkaline phosphatase (ALP) activity, expression of Osterix, ALP and Bone sialoprotein, and matrix calcification. These effects were associated with increased Smad-1 activity, indicating that mitogenic factors interfere with Smad signaling in HMSC differentiation. RTK activate MAPK and inhibit GSK3 through the PI3K/Akt pathway. Biochemical analysis indicated that MAPK JNK and GSK3 especially are potential signaling molecules regulating BMP-induced osteoblastic HMSC differentiation. These observations highlight that the osteogenic effects of BMP2 are modulated by mitogenic factors acting through RTK.