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

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

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1 Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA, USA.
2 Pharmaxis Ltd, Frenchs Forest NSW, Australia.
3 College of Dentistry, Taibah University, Medina, Saudi Arabia.
4 Forsyth Institute, Cambridge, MA, USA.


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.


cell biology; collagen; extracellular matrix; fibroblasts; matrix biology; receptors

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