Tetracycline at subcytotoxic levels inhibits matrix metalloproteinase-2 and -9 but does not remove the smear layer

Yao Wang, Anthony B. Morlandt, Xiaoping Xu, David L. Carnes, Zhihua Chen, Bjorn Steffensen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: The antibacterial and anticollagenolytic properties of tetracycline (TCN) are valuable in periodontal therapy, and TCN treatment can remove the smear layer following root instrumentation. However, recent reports pointing to cytotoxic effects of several acids prompted this study to define TCN concentrations that are anticollagenolytic and remove the smear layer, but have low cytotoxicity. Methods: Human gingival (hGF) and periodontal ligament (hPDL) cells were treated short- (3 minutes) or long-term (24 hours) with TCN to determine concentrations yielding 50% (TD50) and 90% (TD10) cell survival. Activity assays measured TCN concentrations with half-maximal inhibition (IC50) of matrix metalloproteinase-2 and -9 (MMP-2 and -9). Finally, we analyzed the effects of TCN with high (75 mg/ml) or low (1 mg/ml) cytotoxicity on the smear layer by scanning electron microscopy (SEM). Results: The TD50 for TCN after short-term treatment was 4 mg/ml for both hGF and hPDL. Ninety percent of the cells survived 0.2 mg/ml. With long-term treatment, the TD50 for hGF and hPDL was 70 and 30 μg/ml, respectively, and the TD10 was 20 and 5 μg/ml. HGF and hPDL recovered from the 3-minute treatment with 1 mg/ml, but not from concentrations exceeding 3 and 9 mg/ml, respectively. The IC50 was 25 μg/ml for both MMP-2 and MMP-9. Whereas 75 mg/ml TCN removed the smear layer, 1 mg/ml TCN had no effects. Conclusions: Tetracycline has significant cytotoxicity on periodontal cells. Since non-cytotoxic concentrations of TCN inhibited MMP-2 and -9 but had no effects on the smear layer, TCN is not recommended for root surface treatment.

Original languageEnglish (US)
Pages (from-to)1129-1139
Number of pages11
JournalJournal of Periodontology
Volume76
Issue number7
DOIs
StatePublished - Jul 2005

Fingerprint

Smear Layer
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Tetracycline
Periodontal Ligament
Matrix Metalloproteinases
Inhibitory Concentration 50
Electron Scanning Microscopy

Keywords

  • Cytotoxicity
  • Metalloproteinases, matrix
  • Periodontal diseases/drug therapy
  • Periodontal regeneration
  • Smear layer
  • Tetracycline/therapeutic use
  • Tooth root

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Tetracycline at subcytotoxic levels inhibits matrix metalloproteinase-2 and -9 but does not remove the smear layer. / Wang, Yao; Morlandt, Anthony B.; Xu, Xiaoping; Carnes, David L.; Chen, Zhihua; Steffensen, Bjorn.

In: Journal of Periodontology, Vol. 76, No. 7, 07.2005, p. 1129-1139.

Research output: Contribution to journalArticle

Wang, Yao ; Morlandt, Anthony B. ; Xu, Xiaoping ; Carnes, David L. ; Chen, Zhihua ; Steffensen, Bjorn. / Tetracycline at subcytotoxic levels inhibits matrix metalloproteinase-2 and -9 but does not remove the smear layer. In: Journal of Periodontology. 2005 ; Vol. 76, No. 7. pp. 1129-1139.
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abstract = "Background: The antibacterial and anticollagenolytic properties of tetracycline (TCN) are valuable in periodontal therapy, and TCN treatment can remove the smear layer following root instrumentation. However, recent reports pointing to cytotoxic effects of several acids prompted this study to define TCN concentrations that are anticollagenolytic and remove the smear layer, but have low cytotoxicity. Methods: Human gingival (hGF) and periodontal ligament (hPDL) cells were treated short- (3 minutes) or long-term (24 hours) with TCN to determine concentrations yielding 50{\%} (TD50) and 90{\%} (TD10) cell survival. Activity assays measured TCN concentrations with half-maximal inhibition (IC50) of matrix metalloproteinase-2 and -9 (MMP-2 and -9). Finally, we analyzed the effects of TCN with high (75 mg/ml) or low (1 mg/ml) cytotoxicity on the smear layer by scanning electron microscopy (SEM). Results: The TD50 for TCN after short-term treatment was 4 mg/ml for both hGF and hPDL. Ninety percent of the cells survived 0.2 mg/ml. With long-term treatment, the TD50 for hGF and hPDL was 70 and 30 μg/ml, respectively, and the TD10 was 20 and 5 μg/ml. HGF and hPDL recovered from the 3-minute treatment with 1 mg/ml, but not from concentrations exceeding 3 and 9 mg/ml, respectively. The IC50 was 25 μg/ml for both MMP-2 and MMP-9. Whereas 75 mg/ml TCN removed the smear layer, 1 mg/ml TCN had no effects. Conclusions: Tetracycline has significant cytotoxicity on periodontal cells. Since non-cytotoxic concentrations of TCN inhibited MMP-2 and -9 but had no effects on the smear layer, TCN is not recommended for root surface treatment.",
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T1 - Tetracycline at subcytotoxic levels inhibits matrix metalloproteinase-2 and -9 but does not remove the smear layer

AU - Wang, Yao

AU - Morlandt, Anthony B.

AU - Xu, Xiaoping

AU - Carnes, David L.

AU - Chen, Zhihua

AU - Steffensen, Bjorn

PY - 2005/7

Y1 - 2005/7

N2 - Background: The antibacterial and anticollagenolytic properties of tetracycline (TCN) are valuable in periodontal therapy, and TCN treatment can remove the smear layer following root instrumentation. However, recent reports pointing to cytotoxic effects of several acids prompted this study to define TCN concentrations that are anticollagenolytic and remove the smear layer, but have low cytotoxicity. Methods: Human gingival (hGF) and periodontal ligament (hPDL) cells were treated short- (3 minutes) or long-term (24 hours) with TCN to determine concentrations yielding 50% (TD50) and 90% (TD10) cell survival. Activity assays measured TCN concentrations with half-maximal inhibition (IC50) of matrix metalloproteinase-2 and -9 (MMP-2 and -9). Finally, we analyzed the effects of TCN with high (75 mg/ml) or low (1 mg/ml) cytotoxicity on the smear layer by scanning electron microscopy (SEM). Results: The TD50 for TCN after short-term treatment was 4 mg/ml for both hGF and hPDL. Ninety percent of the cells survived 0.2 mg/ml. With long-term treatment, the TD50 for hGF and hPDL was 70 and 30 μg/ml, respectively, and the TD10 was 20 and 5 μg/ml. HGF and hPDL recovered from the 3-minute treatment with 1 mg/ml, but not from concentrations exceeding 3 and 9 mg/ml, respectively. The IC50 was 25 μg/ml for both MMP-2 and MMP-9. Whereas 75 mg/ml TCN removed the smear layer, 1 mg/ml TCN had no effects. Conclusions: Tetracycline has significant cytotoxicity on periodontal cells. Since non-cytotoxic concentrations of TCN inhibited MMP-2 and -9 but had no effects on the smear layer, TCN is not recommended for root surface treatment.

AB - Background: The antibacterial and anticollagenolytic properties of tetracycline (TCN) are valuable in periodontal therapy, and TCN treatment can remove the smear layer following root instrumentation. However, recent reports pointing to cytotoxic effects of several acids prompted this study to define TCN concentrations that are anticollagenolytic and remove the smear layer, but have low cytotoxicity. Methods: Human gingival (hGF) and periodontal ligament (hPDL) cells were treated short- (3 minutes) or long-term (24 hours) with TCN to determine concentrations yielding 50% (TD50) and 90% (TD10) cell survival. Activity assays measured TCN concentrations with half-maximal inhibition (IC50) of matrix metalloproteinase-2 and -9 (MMP-2 and -9). Finally, we analyzed the effects of TCN with high (75 mg/ml) or low (1 mg/ml) cytotoxicity on the smear layer by scanning electron microscopy (SEM). Results: The TD50 for TCN after short-term treatment was 4 mg/ml for both hGF and hPDL. Ninety percent of the cells survived 0.2 mg/ml. With long-term treatment, the TD50 for hGF and hPDL was 70 and 30 μg/ml, respectively, and the TD10 was 20 and 5 μg/ml. HGF and hPDL recovered from the 3-minute treatment with 1 mg/ml, but not from concentrations exceeding 3 and 9 mg/ml, respectively. The IC50 was 25 μg/ml for both MMP-2 and MMP-9. Whereas 75 mg/ml TCN removed the smear layer, 1 mg/ml TCN had no effects. Conclusions: Tetracycline has significant cytotoxicity on periodontal cells. Since non-cytotoxic concentrations of TCN inhibited MMP-2 and -9 but had no effects on the smear layer, TCN is not recommended for root surface treatment.

KW - Cytotoxicity

KW - Metalloproteinases, matrix

KW - Periodontal diseases/drug therapy

KW - Periodontal regeneration

KW - Smear layer

KW - Tetracycline/therapeutic use

KW - Tooth root

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