Combination of simvastatin and bone morphogenetic protein-2 enhances the differentiation of osteoblasts by regulating the expression of phospho-Smad1/5/8
- Authors:
View Affiliations
Affiliations: Department of Periodontics, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Published online on: May 24, 2012 https://doi.org/10.3892/etm.2012.590
-
Pages:
303-306
Metrics: Total
Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
Abstract
Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which catalyzes the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a rate-limiting step in cholesterol synthesis. A number of studies have demonstrated bone-promoting effects when simvastatin is applied locally with different carriers in various animal models. In the prsent study, the dose-dependent impact of simvastatin and bone morphogenetic protein-2 (BMP-2) on the cellular proliferation and differentiation of osteoprecursor cells was evaluated. The alkaline phosphatase activity (ALP) test was performed to assess differentiation, and protein expression related to bone formation, including that of phospho-Smad1/5/8 (pSmad1/5/8), was measured using western blot analysis to evaluate the underlying mechanism(s). Cultures grown in the presence of 0.1 µM simvastatin with 60 ng/ml BMP-2 exhibited the highest value for ALP activity. The results of the western blot analysis indicated that the addition of simvastatin upregulated pSmad1/5/8 expression and the combination of 0.1 µM simvastatin and 60 ng/ml BMP-2 produced a significant increase in protein expression. Based on these findings, it was concluded that the combination of simvastatin and BMP-2 produced positive effects on the differentiation of osteoprecursor cells. The results also suggest that the combination of simvastatin and BMP-2 has synergistic effects that are achieved through the BMP pathway by enhancing the expression of pSmad1/5/8 expression.
View References
1.
|
Chen PY, Sun JS, Tsuang YH, Chen MH, Weng
PW and Lin FH: Simvastatin promotes osteoblast viability and
differentiation via Ras/Smad/Erk/BMP-2 signaling pathway. Nutr Res.
30:191–199. 2010. View Article : Google Scholar : PubMed/NCBI
|
2.
|
Park JB: The use of simvastatin in bone
regeneration. Med Oral Patol Oral Cir Bucal. 14:e485–488.
2009.PubMed/NCBI
|
3.
|
Park JB, Zhang H, Lin CY, et al:
Simvastatin maintains osteoblastic viability while promoting
differentiation by partially regulating the expressions of estrogen
receptors alpha. J Surg Res. 174:278–283. 2012. View Article : Google Scholar
|
4.
|
Maeda T, Matsunuma A, Kawane T and
Horiuchi N: Simvastatin promotes osteoblast differentiation and
mineralization in MC3T3-E1 cells. Biochem Biophys Res Commun.
280:874–877. 2001. View Article : Google Scholar : PubMed/NCBI
|
5.
|
Meleti Z, Shapiro IM and Adams CS:
Inorganic phosphate induces apoptosis of osteoblast-like cells in
culture. Bone. 27:359–366. 2000. View Article : Google Scholar : PubMed/NCBI
|
6.
|
Baek KH, Lee WY, Oh KW, et al: The effect
of simvastatin on the proliferation and differentiation of human
bone marrow stromal cells. J Korean Med Sci. 20:438–444. 2005.
View Article : Google Scholar : PubMed/NCBI
|
7.
|
Moursi AM, Winnard PL, Winnard AV,
Rubenstrunk JM and Mooney MP: Fibroblast growth factor 2 induces
increased calvarial osteoblast proliferation and cranial suture
fusion. Cleft Palate Craniofac J. 39:487–496. 2002. View Article : Google Scholar : PubMed/NCBI
|
8.
|
Park JB: Effects of fibroblast growth
factor 2 on osteoblastic proliferation and differentiation by
regulating bone morphogenetic protein receptor expression. J
Craniofac Surg. 22:1880–1882. 2011. View Article : Google Scholar : PubMed/NCBI
|
9.
|
Lee MH, Kim YJ, Kim HJ, et al:
BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-beta 1
opposes the BMP-2-induced osteoblast differentiation by suppression
of Dlx5 expression. J Biol Chem. 278:34387–34394. 2003. View Article : Google Scholar : PubMed/NCBI
|