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

Jun Sun, Fengyu Song, Weiping Zhang, Brent E. Sexton, L. Windsor

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)728-736
Number of pages9
JournalArchives of Oral Biology
Volume57
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Alendronate
Osteoblasts
Matrix Metalloproteinases
Matrix Metalloproteinase 2
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 14
Matrix Metalloproteinase 1
Conditioned Culture Medium
Collagen
Membranes
Tissue Inhibitor of Metalloproteinases
Poisons
Gelatin
Collagen Type I
Western Blotting
Gels
Cell Proliferation

Keywords

  • Alendronate
  • Bisphosphonate
  • Bisphosphonate related osteonecrosis of the jaw (BRONJ)
  • Matrix metalloproteinases
  • Osteoblast
  • Type I collagen

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Cell Biology
  • Dentistry(all)

Cite this

Effects of alendronate on human osteoblast-like MG63 cells and matrix metalloproteinases. / Sun, Jun; Song, Fengyu; Zhang, Weiping; Sexton, Brent E.; Windsor, L.

In: Archives of Oral Biology, Vol. 57, No. 6, 06.2012, p. 728-736.

Research output: Contribution to journalArticle

Sun, Jun ; Song, Fengyu ; Zhang, Weiping ; Sexton, Brent E. ; Windsor, L. / Effects of alendronate on human osteoblast-like MG63 cells and matrix metalloproteinases. In: Archives of Oral Biology. 2012 ; Vol. 57, No. 6. pp. 728-736.
@article{dd73ea7795234166a8993b85ccb5081b,
title = "Effects of alendronate on human osteoblast-like MG63 cells and matrix metalloproteinases",
abstract = "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.",
keywords = "Alendronate, Bisphosphonate, Bisphosphonate related osteonecrosis of the jaw (BRONJ), Matrix metalloproteinases, Osteoblast, Type I collagen",
author = "Jun Sun and Fengyu Song and Weiping Zhang and Sexton, {Brent E.} and L. Windsor",
year = "2012",
month = "6",
doi = "10.1016/j.archoralbio.2011.12.007",
language = "English (US)",
volume = "57",
pages = "728--736",
journal = "Archives of Oral Biology",
issn = "0003-9969",
publisher = "Elsevier Limited",
number = "6",

}

TY - JOUR

T1 - Effects of alendronate on human osteoblast-like MG63 cells and matrix metalloproteinases

AU - Sun, Jun

AU - Song, Fengyu

AU - Zhang, Weiping

AU - Sexton, Brent E.

AU - Windsor, L.

PY - 2012/6

Y1 - 2012/6

N2 - 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.

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.

KW - Alendronate

KW - Bisphosphonate

KW - Bisphosphonate related osteonecrosis of the jaw (BRONJ)

KW - Matrix metalloproteinases

KW - Osteoblast

KW - Type I collagen

UR - http://www.scopus.com/inward/record.url?scp=84862815521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862815521&partnerID=8YFLogxK

U2 - 10.1016/j.archoralbio.2011.12.007

DO - 10.1016/j.archoralbio.2011.12.007

M3 - Article

VL - 57

SP - 728

EP - 736

JO - Archives of Oral Biology

JF - Archives of Oral Biology

SN - 0003-9969

IS - 6

ER -