Effects of alendronate on human osteoblast-like MG63 cells and matrix metalloproteinases

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• 作者：Jun Sun^a ; ^b ; Fengyu Song^a ; Weiping Zhang^a ; Brent E. Sexton^c ; L. Jack Windsor^a ; ^{ljwindso@iupui.edu}
• 关键词：Osteoblast ; Alendronate ; Bisphosphonate ; Type I collagen ; Matrix metalloproteinases ; Bisphosphonate related osteonecrosis of the jaw (BRONJ)
• 刊名：Archives of Oral Biology
• 出版年：2012
• 期刊代码：25_00039969
• 类别：med
• 出版时间：June, 2012
• 卷：57
• 期：6
• 页码：728-736
• 文件大小：782 K

摘要

Objective

The objective of this study was to examine the effects of alendronate on the expression and activity of matrix metalloproteinases (MMPs) and the expression of the tissue inhibitors of MMPs (TIMPs) from human osteoblast-like MG63 cells.

Materials and methods

MG63 cells were exposed to various concentrations of alendronate. Cell proliferation and cytotoxicity were evaluated by water-soluble tetrazolium-1 and lactate dehydrogenase, respectively. MG63-mediated collagen degradation was assessed utilising Type I collagen assays. Conditioned media and membrane extracts were collected for Western blot analyses of select MMPs and TIMPs. Gelatin zymography gels were incubated with alendronate to assess its effects on MMP-2 activity.

Results

Alendronate affected MG63 proliferation and cytotoxicity at concentrations equal to/or greater than 10^鈭? M (all p < 0.05). There were no significant differences in the collagen degrading ability of treated cells at non-toxic levels vs. untreated cells. Alendronate had no effects on the expression of MMP-2 or MT1-MMP (membrane type-1 MMP) in the conditioned media or membrane extracts, and of MMP-1 or TIMP-2 in the conditioned media. TIMP-2 in the membrane extracts was not detectable. MMP-2 activity in the zymograms was inhibited by 10^鈭? and 10^鈭? M alendronate.

Conclusion

Alendronate at 10^鈭? M or higher was toxic to the cells. Alendronate at 10^鈭? to 10^鈭? M did not alter the expression of MMP-1, MMP-2, MT1-MMP or TIMP-2, as well as did not alter collagen degradation. Alendronate inhibited MMP-2 activity at 10^鈭? and 10^鈭? M in the zymograms. In conclusion, non-toxic levels of alendronate (10^鈭? to 10^鈭? M) did not alter MMP expression in MG63 cells or inhibit MMP-2 activity.