title: The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells.
abstract: Statins have been postulated to affect the bone metabolism. Recent experimental and epidemiologic studies have suggested that statins may also have bone protective effects. This study assessed the effects of simvastatin on the proliferation and differentiation of human bone marrow stromal cells (BMSCs) in an ex vivo culture. The bone marrow was obtained from healthy donors. Mononuclear cells were isolated and cultured to osteoblastic lineage. In the primary culture, 10(-6) M simvastatin diminished the mean size of the colony forming units-fibroblastic (CFU-Fs) and enhanced matrix calcification. At near confluence, the cells were sub-cultured. Thereafter, the alkaline phosphatase (ALP) activities of each group were measured by the time course of the secondary culture. Simvastatin increased the ALP activity in a dose dependent manner, and this stimulatory effect was more evident during the early period of culture. A 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was performed during the secondary culture in order to estimate the effect of simvastatin on the proliferation of human BMSCs. When compared to the control group, simvastatin significantly decreased the proliferation of cells of each culture well. 10(-6) M of simvastatin also significantly enhanced the osteocalcin mRNA expression level. This study shows that simvastatin has a stimulatory effect on bone formation through osteoblastic differentiation, and has an inhibitory effect on the proliferative potential of human BMSCs.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Baek
authors.forename: Won Young
authors.initials: WY
authors.lastname: Lee
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Oh
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Tae
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lee
authors.forename: En Jung
authors.initials: EJ
authors.lastname: Lee
authors.forename: Je Ho
authors.initials: JH
authors.lastname: Han
authors.forename: Moo Il
authors.initials: MI
authors.lastname: Kang
authors.forename: Bong Yun
authors.initials: BY
authors.lastname: Cha
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Ho Young
authors.initials: HY
authors.lastname: Son
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Kang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D019821:Simvastatin; D000469:Alkaline Phosphatase