PMID- 22251575 OWN - NLM STAT- MEDLINE DCOM- 20121029 LR - 20220330 IS - 1879-1506 (Electronic) IS - 0003-9969 (Linking) VI - 57 IP - 6 DP - 2012 Jun TI - Effects of alendronate on human osteoblast-like MG63 cells and matrix metalloproteinases. PG - 728-36 LID - 10.1016/j.archoralbio.2011.12.007 [doi] AB - 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(-5) 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(-3) and 10(-2) M alendronate. CONCLUSION: Alendronate at 10(-5) M or higher was toxic to the cells. Alendronate at 10(-8) to 10(-6) 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(-3) and 10(-2) M in the zymograms. In conclusion, non-toxic levels of alendronate (10(-8) to 10(-6) M) did not alter MMP expression in MG63 cells or inhibit MMP-2 activity. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Sun, Jun AU - Sun J AD - Department of Oral Biology, Indiana University School of Dentistry, Indianapolis, IN 46202, USA. FAU - Song, Fengyu AU - Song F FAU - Zhang, Weiping AU - Zhang W FAU - Sexton, Brent E AU - Sexton BE FAU - Windsor, L Jack AU - Windsor LJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120116 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 RN - 0 (Bone Density Conservation Agents) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - 9007-34-5 (Collagen) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - X1J18R4W8P (Alendronate) SB - IM MH - Alendronate/*pharmacology MH - Analysis of Variance MH - Blotting, Western MH - Bone Density Conservation Agents/*pharmacology MH - Cell Line MH - Cell Proliferation MH - Collagen/metabolism MH - Electrophoresis, Polyacrylamide Gel MH - Humans MH - L-Lactate Dehydrogenase/metabolism MH - Matrix Metalloproteinase 2/*drug effects/*metabolism MH - Osteoblasts/*drug effects MH - Tissue Inhibitor of Metalloproteinase-1/metabolism MH - Tissue Inhibitor of Metalloproteinase-2/metabolism EDAT- 2012/01/19 06:00 MHDA- 2012/10/30 06:00 CRDT- 2012/01/19 06:00 PHST- 2011/07/13 00:00 [received] PHST- 2011/12/16 00:00 [revised] PHST- 2011/12/19 00:00 [accepted] PHST- 2012/01/19 06:00 [entrez] PHST- 2012/01/19 06:00 [pubmed] PHST- 2012/10/30 06:00 [medline] AID - S0003-9969(11)00423-7 [pii] AID - 10.1016/j.archoralbio.2011.12.007 [doi] PST - ppublish SO - Arch Oral Biol. 2012 Jun;57(6):728-36. doi: 10.1016/j.archoralbio.2011.12.007. Epub 2012 Jan 16.