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Alternative model for cathepsin K activation in human dentin.

A Bafail1, M Azizalrahman2, T Vilde2

  • 1Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada; Department of Restorative Dental Sciences, Faculty of Dentistry, Taibah University, Medina, Saudi Arabia.

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Lactic acid (LA) activates endogenous cathepsin K (CT-K) in dentin, leading to collagen degradation. This study establishes an LA model for investigating CT-K inhibitors in dentin.

Keywords:
CollagenCysteine cathepsinsDegradationDentinLactic acid

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Area of Science:

  • Biomaterials Science
  • Dental Research
  • Biochemistry

Background:

  • Dentin collagen degradation is a significant concern in restorative dentistry.
  • Understanding endogenous protease activity, like cathepsin K (CT-K), is crucial for developing effective inhibitors.
  • Lactic acid (LA) and polyacrylic acid (PAA) are common challenges to dentin, but their effects on CT-K activity differ.

Purpose of the Study:

  • To evaluate protease activity in dentin matrices using lactic acid (LA) and polyacrylic acid (PAA) challenge models.
  • To compare the effectiveness of LA and PAA in degrading dentin collagen at the optimal pH for cathepsin K (CT-K).
  • To assess the potential of an LA-based model for studying CT-K activity and inhibitors in human dentin.

Main Methods:

  • Demineralized human dentin disks were challenged with LA, PAA, artificial saliva (AS), or deionized water (C) for 24 hours and 7 days.
  • Dentin collagen degradation was assessed by measuring changes in dry mass, ultimate tensile strength (UTS), and the release of specific telopeptides (ICTP, CTX) indicative of protease activity.
  • Incubation media were analyzed for telopeptide release, correlating with matrix metalloproteinases (MMPs) and CT-K activities.

Main Results:

  • Lactic acid (LA) induced significantly higher weight loss in dentin compared to controls.
  • Ultimate tensile strength (UTS) was significantly reduced in LA and PAA groups compared to artificial saliva (AS) and control (C) groups.
  • Telopeptide assays showed significantly higher CTX release in the LA group, indicating activation of CT-K by LA.

Conclusions:

  • Lactic acid (LA) activates endogenous cathepsin K (CT-K) in dentin, as evidenced by increased CTX release.
  • The LA challenge model effectively demonstrates dentin collagen degradation and CT-K activation.
  • This LA-based model holds potential for future research on CT-K activity and the development of inhibitors for human dentin.