title: The effect of simvastatin on chemotactic capability of SDF-1α and the promotion of bone regeneration.
abstract: The purpose of this study was to investigate the cooperative effects of simvastatin (SIM) and stromal cell-derived factor-1α (SDF-1α) on the osteogenic and migration capabilities of mesenchymal stem cells (MSCs), and construct a cell-free bone tissue engineering system comprising SIM, SDF-1α and scaffold. We found that 0.2 μm SIM significantly increased alkaline phosphatase activity (P < 0.05) of mouse bone marrow MSCs with no inhibition of cell proliferation, and enhanced the chemotactic capability of SDF-1α (P < 0.05). Next, we constructed a novel cell-free bone tissue engineering system using PLGA loaded with SIM and SDF-1α, and applied it in critical-sized calvarial defects in mice. New bone formation in the defect was evaluated by micro-CT, HE staining and immunohistochemistry. The results showed that PLGA loaded with SIM and SDF-1α promoted bone regeneration significantly more than controls. We investigated possible mechanisms, and showed that SDF-1α combined with SIM increased MSC migration and homing in vivo, promoted angiogenesis and enhanced the expression of BMP-2 in newly-formed bone tissue. In conclusion, SIM enhanced the chemotactic capability of SDF-1α and the cell-free bone tissue engineering system composed of SIM, SDF-1α and scaffold promoted bone regeneration in mouse critical-sized calvarial defects.
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Yun-Song
authors.initials: YS
authors.lastname: Liu
authors.affiliation: The 3rd Dental Clinic, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Meng-En
authors.initials: ME
authors.lastname: Ou
authors.affiliation: The Core Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gu
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Long-Wei
authors.initials: LW
authors.lastname: Lv
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Xiang-Hui
authors.initials: XH
authors.lastname: Zhao
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Chan-Yuan
authors.initials: CY
authors.lastname: Jin
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The 3rd Dental Clinic, Peking University School and Hospital of Stomatology, Beijing 100081, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China; National Engineering Lab for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing 100081, China. Electronic address: kqzhouysh@hsc.pku.edu.cn.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Zhou
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000008:administration & dosage / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D012886:Skull / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D054377:Chemokine CXCL12; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000469:Alkaline Phosphatase
keywords: Bone healing; Cell homing; Simvastatin; Stromal cell-derived factor 1