title: The stimulation of osteogenic differentiation of mesenchymal stem cells and vascular endothelial growth factor secretion of endothelial cells by β-CaSiO3/β-Ca3(PO4)2 scaffolds.
abstract: Porous β-CaSiO3/β-Ca3(PO4)2 (β-CS/β-TCP) composite scaffolds have been previously shown to promote bone formation in vivo. However, the mechanisms underlying such beneficial effects remain unclear. In this study, we recreated an extracellular environment using the extracts of β-CS/β-TCP composites developed in our previous in vivo study, and investigated the effects of the extracts on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and its related mechanisms. The angiogenic potential of the extracts was also evaluated using human umbilical vein endothelial cells (HUVECs). In the absence of osteogenic supplements, the osteogenic differentiation of rBMSCs was detected by alkaline phosphatase (ALP) activity assay and the messenger RNA expression of a panel of osteoblast markers. The results showed that the soluble ions of porous β-CS/β-TCP composites were capable of promoting cell viability, directly inducing cell differentiation. The increase in phosphorylation of AMP-activated protein kinase (AMPK) and ERK1/2 were observed in rBMSCs cultured in β-CS/β-TCP composite extracts. The ALP expression, calcium deposition, and ERK1/2 phosphorylation of rBMSCs, which was promoted by ions released from β-CS/β-TCP composites, were blocked by an AMPK inhibitor, Compound C. These results indicate that bioactive ions extracted from β-CS/β-TCP composites could stimulate the osteogenic differentiation of rBMSCs via the AMPK-Erk1/2 pathway. Interestingly, the secretion of vascular endothelial growth factor and the viability of HUVECs were shown to be enhanced in the presence of extracts from the β-CS/β-TCP composite scaffolds. Our findings suggest that 50 or 80% wt. CS could promote bone regeneration by stimulating osteogenesis and angiogenesis.
authors.affiliation: Shanghai Biomaterials Research & Testing Center, Shanghai Key Laboratory of Stomatolog, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200023, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Kaili
authors.initials: K
authors.lastname: Lin
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.forename: Jiao
authors.initials: J
authors.lastname: Sun
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000166:cytology*; D017610:Calcium Compounds; D002130:Calcium Phosphates; D002454:Cell Differentiation; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D017640:Silicates; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D017610:Calcium Compounds; D002130:Calcium Phosphates; D017931:DNA Primers; D017640:Silicates; D042461:Vascular Endothelial Growth Factor A; C020243:calcium phosphate; D000263:Adenylate Kinase; C031293:calcium silicate
keywords: AMPK; bioactive ions; calcium silicate; osteogenic differentiation; tricalcium phosphate