Activation of PKA/CREB Signaling is Involved in BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Hongyu ZhangJinyong Luo

Abstract

BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cells (MSCs) although the molecular mechanism involved is largely unknown. Here, we explored the detail role of PKA/CREB signaling in BMP9-induced osteogenic differentiation. Activation status of PKA/CREB signaling is assessed by nonradioactive assay and Western blot. Using PKA inhibitors and a dominant negative protein of CREB (A-CREB), we investigated the effect of PKA/CREB signaling on BMP9-induced osteogenic differentiation. We found that BMP9 promotes PKA activity and enhances CREB phosphorylation in MSCs. BMP9 is shown to down-regulate protein kinase A inhibitor γ (PKIγ) expression. We demonstrated that PKA inhibitors suppress BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs as well as late osteogenic markers osteopontin (OPN), osteocalcin (OCN) and matrix mineralization. We found that PKA inhibitor reduces BMP9-induced Runx2 activation and p38 phosphorylation in MSCs. Lastly, interference of CREB function by A-CREB decreased BMP9-induced osteogenic differentiation as well. Our results revealed that BMP9 may activate PKA/CREB signaling in MSCs through suppression of PKIγ expression. It is noteworthy that inhi...Continue Reading

Citations

Dec 18, 2018·Journal of Cellular Biochemistry·Yuan WangJian-Gang Shi
Nov 2, 2019·Cell Death & Disease·Min Kyung KimHong-Hee Kim
Dec 1, 2020·Journal of Biomedical Materials Research. Part a·Hyang-Seon RoYoung-Kwon Seo
Feb 7, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Angshuman Bharadwaz, Ambalangodage C Jayasuriya
Feb 7, 2021·International Journal of Biological Macromolecules·Wen-Di ShenJian-Ping Luo
Sep 27, 2021·Pflügers Archiv : European journal of physiology·Barbara MoserJakob Voelkl

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