TY - JOUR
T1 - A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells
AU - Barradas, Ana M.C.
AU - Fernandes, Hugo A.M.
AU - Groen, Nathalie
AU - Chai, Yoke Chin
AU - Schrooten, Jan
AU - van de Peppel, Jeroen
AU - Van Leeuwen, Johannes P.T.M.
AU - Van Blitterswijk, Clemens A.
AU - de Boer, Jan
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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 invitro 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.
AB - 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 invitro 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.
KW - Bone morphogenetic protein
KW - Calcium phosphate
KW - Osteogenesis
KW - Stem cell
UR - http://www.scopus.com/inward/record.url?scp=84856576550&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2012.01.020
DO - 10.1016/j.biomaterials.2012.01.020
M3 - Article
C2 - 22285104
AN - SCOPUS:84856576550
SN - 0142-9612
VL - 33
SP - 3205
EP - 3215
JO - Biomaterials
JF - Biomaterials
IS - 11
ER -