title: Bone morphogenetic protein Smads signaling in mesenchymal stem cells affected by osteoinductive calcium phosphate ceramics.
abstract: Porous calcium phosphate ceramics (CaP ceramics) could induce ectopic bone formation which was regulated by various signal molecules. In this work, bone marrow mesenchymal stem cells (MSCs) were cultured on the surface of osteoinductive hydroxyapatite (HA) and biphasic calcium phosphate (BCP) ceramics in comparison with control (culture plate) for up to 14 days to detect the signal molecules which might be affected by the CaP ceramics. Without adding osteogenic factors, MSCs cultured on HA and BCP both expressed higher Runx2, Osterix, collagen type I, osteopontin, bone sialoprotein, and osteocalcin at various stages compared with control, thus confirmed the osteoblastic differentiation of MSCs. Later study demonstrated the messenger RNA level of bone morphogenetic protein 2 (BMP2) and BMP4 were also significantly enhanced by HA and BCP. Furthermore, Smad1, 4, 5, and Dlx5, the main molecules in the BMP/Smads signaling pathway, were upregulated by HA and BCP. Moreover, the higher expression of Smads and BMP2, 4 in BCP over HA, corresponded to the better performance of BCP in stimulating in vitro osteoblastic differentiation of MSCs. This was in accordance with the better osteoinductivity of BCP over HA in vivo. Altogether, these results implied that the CaP ceramics may initiate the osteoblastic differentiation of MSCs by influencing the expression of molecules in BMP/Smads pathway.
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors.forename: Zhurong
authors.initials: Z
authors.lastname: Tang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Fangzhu
authors.initials: F
authors.lastname: Qing
authors.forename: Yilu
authors.initials: Y
authors.lastname: Ni
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Fan
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Tan
authors.forename: Xingdong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002130:Calcium Phosphates / Q000737:chemistry*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002516:Ceramics / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D005786:Gene Expression Regulation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010006:Osteoblasts / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051785:Smad Proteins / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D002130:Calcium Phosphates; D012333:RNA, Messenger; D051785:Smad Proteins; D017886:Durapatite; C020243:calcium phosphate
keywords: BMP signaling; Smads pathway; calcium phosphate ceramics; osteoblastic differentiation; osteoinduction