TY - JOUR
T1 - Molecular mechanisms of biomaterial-driven osteogenic differentiation in human mesenchymal stromal cells
AU - Barradas, A.M.C.
AU - Monticone, V.
AU - Hulsman, M.
AU - Danoux, Charlene
AU - Fernandes, H.A.M.
AU - Tahmasebi Birgani, Zeinab
AU - Barrere-de Groot, F.YF.
AU - Yuan, Huipin
AU - Reinders, M.J.T.
AU - Habibovic, Pamela
AU - van Blitterswijk, Clemens
AU - de Boer, Jan
PY - 2013/5/10
Y1 - 2013/5/10
N2 - Calcium phosphate (CaP) based ceramics are used as bone graft substitutes in the treatment of bone defects. The physico-chemical properties of these materials determine their bioactivity, meaning that molecular and cellular responses in the body will be tuned accordingly. In a previous study, we compared two porous CaP ceramics, hydroxyapatite (HA) and β-tricalcium phosphate (TCP), which, among other properties, differ in their degradation behaviour in vitro and in vivo, and we demonstrated that the more degradable β-TCP induced more bone formation in a heterotopic model in sheep. This is correlated to in vitro data, where human bone marrow derived mesenchymal stromal cells (MSC) exhibited higher expression of osteogenic differentiation markers, such as osteopontin, osteocalcin and bone sialoprotein, when cultured in β-TCP than in HA. More recently, we also showed that this effect could be mimicked in vitro by exposure of MSC to high concentrations of calcium ions (Ca2+). To further correlate surface physico-chemical dynamics of HA and β-TCP ceramics with the molecular response of MSC, we followed Ca2+ release and surface changes in time as well as cell attachment and osteogenic differentiation of MSC on these ceramics. Within 24 hours, we observed differences in cell morphology, with MSC cultured in β-TCP displaying more pronounced attachment and spreading than cells cultured in HA. In the same time frame, β-TCP induced expression of G-protein coupled receptor (GPCR) 5A and regulator of G-protein signaling 2, revealed by DNA microarray analysis. These genes, associated with the protein kinase A and GPCR signaling pathways, may herald the earliest response of MSC to bone-inducing ceramics.
AB - Calcium phosphate (CaP) based ceramics are used as bone graft substitutes in the treatment of bone defects. The physico-chemical properties of these materials determine their bioactivity, meaning that molecular and cellular responses in the body will be tuned accordingly. In a previous study, we compared two porous CaP ceramics, hydroxyapatite (HA) and β-tricalcium phosphate (TCP), which, among other properties, differ in their degradation behaviour in vitro and in vivo, and we demonstrated that the more degradable β-TCP induced more bone formation in a heterotopic model in sheep. This is correlated to in vitro data, where human bone marrow derived mesenchymal stromal cells (MSC) exhibited higher expression of osteogenic differentiation markers, such as osteopontin, osteocalcin and bone sialoprotein, when cultured in β-TCP than in HA. More recently, we also showed that this effect could be mimicked in vitro by exposure of MSC to high concentrations of calcium ions (Ca2+). To further correlate surface physico-chemical dynamics of HA and β-TCP ceramics with the molecular response of MSC, we followed Ca2+ release and surface changes in time as well as cell attachment and osteogenic differentiation of MSC on these ceramics. Within 24 hours, we observed differences in cell morphology, with MSC cultured in β-TCP displaying more pronounced attachment and spreading than cells cultured in HA. In the same time frame, β-TCP induced expression of G-protein coupled receptor (GPCR) 5A and regulator of G-protein signaling 2, revealed by DNA microarray analysis. These genes, associated with the protein kinase A and GPCR signaling pathways, may herald the earliest response of MSC to bone-inducing ceramics.
KW - METIS-296611
KW - IR-86191
U2 - 10.1039/C3IB40027A
DO - 10.1039/C3IB40027A
M3 - Article
SN - 1757-9694
VL - 5
SP - 920
EP - 931
JO - Integrative biology
JF - Integrative biology
IS - 7
ER -