Effect of low-level laser therapy on oral keratinocytes exposed to bisphosphonate

Lasers Med Sci. 2015 Feb;30(2):635-43. doi: 10.1007/s10103-013-1382-6. Epub 2013 Jul 9.


Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate therapy. However, its pathophysiology is not yet fully elucidated, and effective treatment of BRONJ remains unclear. The aim of this study is to investigate the effects of alendronate on oral keratinocytes and of low-level laser therapy (LLLT) on alendronate-treated keratinocytes, specifically by evaluating their viability, apoptosis, and wound healing function after irradiation. Oral keratinocyte cells (HaCaT) were exposed to 25 μM alendronate. Then, laser irradiation was performed with a low-level Ga-Al-As laser (λ = 808 ± 3 nm, 80 mW, and 80 mA; NDLux, Seoul, Korea) using 1.2 J/cm(2) energy dose. Viability was analyzed using MTT assay. Apoptosis was measured by Hoechst staining, caspase assay. Changes in secretion of IL-8, VEGF, and collagen type I were studied by ELISA and immunofluorescence microscopy. Scratch wound assays were also performed to measure cellular migration. Our results show that alendronate inhibits keratinocyte viability, expression of IL-8, VEGF, and collagen type I which are intimately related to healing events and cell migration while promoting apoptosis. Our results serve to demonstrate the utility of LLLT in partially overcoming the inhibitory effects of this bisphosphonate. From these results, the authors believe that the present study will provide an experimental basis for a fuller explanation of the clinical effects of LLLT as a BRONJ treatment modality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / chemistry
  • Apoptosis / drug effects
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / surgery
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Collagen Type I / metabolism
  • Diphosphonates / chemistry*
  • Humans
  • Interleukin-8 / metabolism
  • Keratinocytes / drug effects*
  • Low-Level Light Therapy / methods*
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*


  • Collagen Type I
  • Diphosphonates
  • Interleukin-8
  • Vascular Endothelial Growth Factor A
  • Alendronate