PMID- 20939484 OWN - NLM STAT- MEDLINE DCOM- 20110111 LR - 20161125 IS - 1002-1892 (Print) IS - 1002-1892 (Linking) VI - 24 IP - 9 DP - 2010 Sep TI - [Effect of simvastatin on inducing endothelial progenitor cells homing and promoting bone defect repair]. PG - 1103-6 AB - OBJECTIVE: To investigate the effect of simvastatin on inducing endothelial progenitor cells (EPCs) homing and promoting bone defect repair, and to explore the mechanism of local implanting simvastatin in promoting bone formation. METHODS: Simvastatin (50 mg) compounded with polylactic acid (PLA, 200 mg) or only PLA (200 mg) was dissolved in acetone (1 mL) to prepare implanted materials (Simvastatin-PLA material, PLA material). EPCs were harvested from bone marrow of 2 male rabbits and cultured with M199; after identified by immunohistochemistry, the cell suspension of EPCs at the 3rd generation (2 x 10(6) cells/mL) was prepared and transplanted into 12 female rabbits through auricular veins (2 mL). After 3 days, the models of cranial defect with 15 cm diameter were made in the 12 female rabbits. And the defects were repaired with Simvastatin-PLA materials (experimental group, n=6) and PLA materials (control group, n=6), respectively. The bone repair was observed after 8 weeks of operation by gross appearance, X-ray film, and histology; gelatin-ink perfusion and HE staining were used to show the new vessels formation in the defect. Fluorescence in situ hybridization (FISH) was performed to show the EPCs homing at the defect site. RESULTS: All experimental animals of 2 groups survived to the end of the experiment. After 8 weeks in experimental group, new bone formation was observed in the bone defect by gross and histology, and an irregular, hyperdense shadow by X-ray film; no similar changes were observed in control group. FISH showed that the male EPC containing Y chromosome was found in the wall of new vessels in the defect of experimental group, while no male EPC containing Y chromosome was found in control group. The percentage of new bone formation in defect area was 91.63% +/- 4.07% in experimental group and 59.45% +/- 5.43% in control group, showing significant difference (P < 0.05). CONCLUSION: Simvastatin can promote bone defect repair, and its mechanism is probably associated with inducing EPCs homing and enhancing vasculogenesis. FAU - Song, Quansheng AU - Song Q AD - Department of Orthopaedics, Third Hospital, Peking University, Beijing, 100191, PR China. FAU - Wang, Lingying AU - Wang L FAU - Zhu, Jinglin AU - Zhu J FAU - Han, Xiaoguang AU - Han X FAU - Li, Xu AU - Li X FAU - Yang, Yanlin AU - Yang Y FAU - Sun, Yan AU - Sun Y FAU - Song, Chunli AU - Song C LA - chi PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi JT - Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery JID - 9425194 RN - 0 (Polyesters) RN - 0 (Polymers) RN - 33X04XA5AT (Lactic Acid) RN - 459TN2L5F5 (poly(lactide)) RN - AGG2FN16EV (Simvastatin) SB - IM MH - Animals MH - Bone Regeneration/*drug effects MH - Cells, Cultured MH - Endothelial Cells/cytology/*drug effects MH - Female MH - Lactic Acid/pharmacology MH - Male MH - Polyesters MH - Polymers/pharmacology MH - Rabbits MH - Simvastatin/*pharmacology MH - Stem Cells/cytology/*drug effects MH - Tissue Engineering EDAT- 2010/10/14 06:00 MHDA- 2011/01/12 06:00 CRDT- 2010/10/14 06:00 PHST- 2010/10/14 06:00 [entrez] PHST- 2010/10/14 06:00 [pubmed] PHST- 2011/01/12 06:00 [medline] PST - ppublish SO - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010 Sep;24(9):1103-6.