Regulation of BMP2-induced intracellular calcium increases in osteoblasts

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Wenfeng XuXiaoling Liao

Abstract

Although bone morphogenetic protein-2 (BMP2) is a well-characterized regulator that stimulates osteoblast differentiation, little is known about how it regulates intracellular Ca2+ signaling. In this study, intracellular Ca2+ concentration ([Ca2+ ]i ) upon BMP2 application, focal adhesion kinase (FAK) and Src activities were measured in the MC3T3-E1 osteoblast cell line using fluorescence resonance energy transfer-based biosensors. Increase in [Ca2+ ]i , FAK, and Src activities were observed during BMP2 stimulation. The removal of extracellular calcium, the application of membrane channel inhibitors streptomycin or nifedipine, the FAK inhibitor PF-573228 (PF228), and the alkaline phosphatase (ALP) siRNA all blocked the BMP2-stimulated [Ca2+ ]i increase, while the Src inhibitor PP1 did not. In contrast, a gentle decrease of endoplasmic reticulum calcium concentration was found after BMP2 stimulation, which could be blocked by both streptomycin and PP1. Further experiments revealed that BMP2-induced FAK activation could not be inhibited by PP1, ALP siRNA or the calcium channel inhibitor nifedipine. PF228, but not PP1 or calcium channel inhibitors, suppressed ALP elevation resulting from BMP2 stimulation. Therefore, our results su...Continue Reading

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Citations

Mar 23, 2017·The Journal of Clinical Endocrinology and Metabolism·Emma A WebbWolfgang Högler
Dec 30, 2017·Bone Research·Chengde GaoCijun Shuai
Mar 14, 2020·Tissue Engineering. Part a·Wai Myo MaungShinji Kuroda

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