Simvastatin maintains osteoblastic viability while promoting differentiation by partially regulating the expressions of estrogen receptors α

Jun Beom Park, Huina Zhang, Chia Ying Lin, Chong Pyoung Chung, Youngro Byun, Yoon Shin Park, Victor C. Yang

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Background: Statin is a specific inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme involved in the cholesterol synthesis pathway. In addition to their long-known efficacy for lowering cholesterol, statins have also been reported to possess anabolic effects on bone. Simvastatin is reported to increase cancellous bone volume, bone formation rate, and cancellous bone compressive strength in vivo. Materials and Methods: In this report, the effects of simvastatin on osteoprecursor cells were evaluated. The effect on cell viability was determined by MTT assay, whereas differentiation and mineralization were examined using an alkaline phosphatase activity (ALP) test and alizarin red-S staining. Protein expressions related to bone formation, such as estrogen receptor-alpha (ER-α) and beta (ER-β), were evaluated by using a Western blot analysis. To assess whether the osteoinductive effect of simvastatin occurs via estrogen receptor pathway, estrogen receptor agonist (E2) and antagonists (ICI 182,780) were applied to the cultures. Results: Cultures grown in the presence of simvastatin exhibited an increased value for ALP activity and mineralization. The results of the Western blot analysis indicated that the addition of simvastatin up-regulated ER-α and ER-β expression with a statistically significant difference in ER-α expression. Treatment of E2 led to an increase of the ALP activity and mineralization, but addition of the estrogen receptor antagonist ICI 182,780 revealed a decrease in both values. Conclusions: Based on these findings, it was concluded that simvastatin could produce positive effects on both the differentiation and mineralization of osteoprecursor cells. Our results also suggested that osteoinductive effects of simvastatin were achieved through ER pathway via the increase of ER-α expression.

Original languageEnglish
Pages (from-to)278-283
Number of pages6
JournalJournal of Surgical Research
Volume174
Issue number2
DOIs
StatePublished - 15 May 2012

Bibliographical note

Funding Information:
This study was supported in part by NIH Grant R01AR056649 . The research was also sponsored partially by the World Class University (WCU) program through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science, and Technology ( R31-2008-000-10103-01 ). Both VCY and YB are currently WCU faculty members in the Department of Molecular Medicine and Biopharmaceutical Sciences, College of Medicine/College of Pharmacy, Seoul National University, South Korea.

Keywords

  • differentiation
  • estrogen receptor
  • mineralization
  • osteoblast
  • simvastatin

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