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Title: A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells
Authors: Barradas, Ana M C ×
Fernandes, Hugo A M
Groen, Nathalie
Chai, Yoke Chin
Schrooten, Jan
van de Peppel, Jeroen
van Leeuwen, Johannes P T M
van Blitterswijk, Clemens A
de Boer, Jan #
Issue Date: 29-Jan-2012
Publisher: IPC Science and Technology Press
Series Title: Biomaterials vol:33 issue:11 pages:3205-3215
Abstract: The response of osteoprogenitors to calcium (Ca(2+)) is of primary interest for both normal bone homeostasis and the clinical field of bone regeneration. The latter makes use of calcium phosphate-based bone void fillers to heal bone defects, but it is currently not known how Ca(2+) released from these ceramic materials influences cells in situ. Here, we have created an in vitro environment with high extracellular Ca(2+) concentration and investigated the response of human bone marrow-derived mesenchymal stromal cells (hMSCs) to it. Ca(2+) enhanced proliferation and morphological changes in hMSCs. Moreover, the expression of osteogenic genes is highly increased. A 3-fold up-regulation of BMP-2 is observed after only 6h and pharmaceutical interference with a number of proteins involved in Ca(2+) sensing showed that not the calcium sensing receptor, but rather type L voltage-gated calcium channels are involved in mediating the signaling pathway between extracellular Ca(2+) and BMP-2 expression. MEK1/2 activity is essential for the effect of Ca(2+) and using microarray analysis, we have identified c-Fos as an early Ca(2+) response gene. We have demonstrated that hMSC osteogenesis can be induced via extracellular Ca(2+), a simple and economic way of priming hMSCs for bone tissue engineering applications.
ISSN: 0142-9612
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cell and Gene Therapy Applications (-)
Surface and Interface Engineered Materials
× corresponding author
# (joint) last author

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