Multiple Functions of Lysyl Oxidase Like-2 in Oral Fibroproliferative Processes

J Dent Res. 2018 Oct;97(11):1277-1284. doi: 10.1177/0022034518775971. Epub 2018 May 22.


Gingival overgrowth is a side effect of certain medications, including calcium channel blockers, cyclosporin A, and phenytoin. Phenytoin-induced gingival overgrowth is fibrotic. Lysyl oxidases are extracellular enzymes that are required for biosynthetic cross-linking of collagens, and members of this enzyme family are upregulated in fibrosis. Previous studies in humans and in a mouse model of phenytoin-induced gingival overgrowth have shown that LOXL2 is elevated in the epithelium and connective tissue in gingival overgrowth tissues and not in normal tissues. Here, using a novel LOXL2 isoform-selective inhibitor and knockdown studies in loss- and gain-of-function studies, we investigated roles for LOXL2 in promoting cultures of human gingival fibroblasts to proliferate and to accumulate collagen. Data indicate that LOXL2 stimulates gingival fibroblast proliferation, likely by a platelet-derived growth factor B receptor-mediated mechanism. Moreover, collagen accumulation was stimulated by LOXL2 enzyme and inhibited by LOXL2 inhibitor or gene knockdown. These studies suggest that LOXL2 could serve as a potential therapeutic target to address oral fibrotic conditions.

Keywords: cell biology; collagen; extracellular matrix; fibroblasts; matrix biology; receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Oxidoreductases / physiology*
  • Blotting, Western
  • Cell Proliferation / physiology*
  • Cells, Cultured
  • Collagen / metabolism
  • Female
  • Fibroblasts / physiology*
  • Gene Knockdown Techniques
  • Gingiva / growth & development*
  • Gingiva / physiology
  • Humans
  • Receptor, Platelet-Derived Growth Factor beta / metabolism


  • Collagen
  • Amino Acid Oxidoreductases
  • LOXL2 protein, human
  • Receptor, Platelet-Derived Growth Factor beta