Low zoledronate concentrations stimulate human keratinocyte proliferation

Area of Science:

• Dermatology
• Cell Biology
• Pharmacology

Background:

• Zoledronate is a bisphosphonate primarily used for osteoporosis.
• Its role in epithelial regeneration is largely unexplored.
• Keratinocyte behavior is crucial for wound healing and skin barrier function.

Purpose of the Study:

• To investigate the effects of zoledronate on keratinocyte proliferation, migration, and gene expression in an in vitro wound healing model.
• To elucidate the mechanisms underlying zoledronate's impact on cellular behavior.

Main Methods:

• Human keratinocytes (HaCaT) were treated with varying concentrations of zoledronate.
• Cell proliferation was assessed using a fluorescent assay.
• Gene expression of cytokeratin 5 and filaggrin was analyzed.
• In vitro wound healing and matrix metalloproteinase (MMP) activity were evaluated.

Main Results:

• Zoledronate significantly stimulated keratinocyte proliferation.
• Upregulation of cytokeratin 5 and downregulation of filaggrin expression were observed.
• Zoledronate reduced wound healing ability, primarily through increased proliferation rather than enhanced migration.
• No significant effect on MMP-9 activity was detected.

Conclusions:

• Zoledronate promotes keratinocyte proliferation, potentially via reduction of farnesyl pyrophosphate.
• The findings suggest novel therapeutic applications for zoledronate in epithelial regeneration and wound healing.
• Further research is warranted to explore clinical translation.