The role of simvastatin in the osteogenesis of injectable tissue-engineered bone based on human adipose-derived stromal cells and platelet-rich plasma.
An injectable tissue-engineered bone (ITB) composed of human adipose-derived stromal cells (hADSCs) and platelet-rich plasma (hPRP) was preliminarily constructed, but its osteogenic capability needs improving. This study aimed to evaluate if simvastatin can be applied as a bone anabolic agent for this ITB. We found 0.01 microm, 0.1 microm, and 1 microm simvastatin could induce hADSCs' osteoblastic differentiation in vitro that accompanied with non-inhibition on cell proliferation, high alkaline phosphatase activity, more mineralization deposition and more expression of osteoblast-related genes such as osteocalcin, core binding factor alpha1, bone morphogenetic protein-2, vascular endothelial growth factor, and basic fibroblast growth factor. Simvastatin at 1 mum seemed the most optimal concentration due to its high osteocalcin secretion in media (P < 0.01). Quantitative mineralization assay also showed 1 microm SIM had the most obvious synergistic effect on hPRP's induction for matrix mineralization of hADSCs (P < 0.01). When 1 microm Simvastatin was applied to this ITB to restore the critical-sized calvarial defects in mice, more bone formation was observed in defected regions, and the peripheries just outside the defect margins by X-ray analysis, and H&E staining. These findings indicate that simvastatin at optimal concentrations can be used to promote this ITB's osteogenesis. However, simvastatin's effects on this ITB await long-term investigation.
Zhou
Yongsheng
Y
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, PR China. kqzhouysh@hsc.pku.edu.cn
Ni
Yongwei
Y
Liu
Yunsong
Y
Zeng
Baijin
B
Xu
Yongwei
Y
Ge
Wenshu
W
D000273:Adipose Tissue / Q000166:cytology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007267:Injections; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D053657:Platelet-Rich Plasma / Q000378:metabolism*; D011859:Radiography; D019821:Simvastatin / Q000494:pharmacology*; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D013194:Staining and Labeling; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D023822:Tissue Engineering / Q000379:methods*; D055815:Young Adult
D003470:Culture Media; D015675:Osteocalcin; D019821:Simvastatin; D000469:Alkaline Phosphatase