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Molecular and tissue responses in the healing of rat calvarial defects after local application of simvastatin combined with alpha tricalcium phosphate
Author(s) -
Nyan Myat,
Miyahara Takayuki,
Noritake Kanako,
Hao Jia,
Rodriguez Reena,
Kuroda Shinji,
Kasugai Shohei
Publication year - 2010
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.31559
Subject(s) - simvastatin , calvaria , alpha (finance) , andrology , chemistry , endocrinology , medicine , surgery , biochemistry , in vitro , construct validity , patient satisfaction
We have previously reported that healing of rat calvarial defects was enhanced by application of alpha tricalcium phosphate (αTCP) combined with simvastatin, a cholesterol synthesis inhibitor. The purpose of the present study was to investigate the cellular and molecular mechanisms in this phenomenon. Rat calvarial defects were grafted with αTCP with or without simvastatin or left untreated. Animals were sacrificed on 3, 7, 10, 14, and 21 days postoperatively and histological changes in the defect region were assessed. Gene expression patterns were examined by RT‐PCR. Proliferation and migration of osteoprogenitor cells from the dura mater were increased in simvastatin group from day 3 to day 10 ( p < 0.01). New bone formation was significantly increased in simvastatin group on day 14 and day 21 ( p < 0.01). BMP‐2 expression was significantly higher in simvastatin group on day 3 and day 14 ( p < 0.05) and maintained until day 21. Increased upregulation of TGF‐β1 was also observed in the simvastatin group on day 7 ( p < 0.05) which was maintained until day 14. These findings suggest that the proliferation and recruitment of osteoprogenitor cells were critical steps in early stage of bone healing and that these steps were enhanced by TGF‐β1 and BMP‐2, which were stimulated by simvastatin. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010