Nifedipine Induces Gingival Overgrowth in Rats Through a Reduction in Collagen Phagocytosis by Gingival Fibroblasts

Abstract

These findings suggest that the decrease in collagen degradation due to lower phagocytosis is closely associated with the increase in Type I collagen accumulation in nifedipine-treated rat gingiva.

Drug-Induced Gingival Overgrowth—a Review

“…2), and severe inhibition was observed in cyclosporine A-induced gingival overgrowth. 25,26) Interestingly, type I collagen and collagenase mRNA expressions were significantly suppressed by cyclosporin A and nifedipine administration in these rat experimental models. 25,26) From these results, drug-induced gingival overgrowth is not due to the increased synthesis of type I collagen but the decreased degradation of type I collagen in gingival connective tissue through the reduction of collagen phagocytosis of fibroblasts.…”

“…[36][37][38][39] These drug-induced gingival overgrowth is shown to be induced by the excessive accumulation of type I collagen in gingival connective tissue by immunohistochemical analysis with rat experimental models. 25,26) These disorders are therefore suitable to be considered as fibrosis in gingival connective tissue. "Gingival overgrowth" or "gingival enlargement" is the preferred term for all drug-related gingival lesions previously termed "gingival hypertrophy" or "gingival hyperplasia".…”

“…In a rat experimental model, the mRNA expression of both type I collagen and collagenase in vivo is significantly lower in overgrown gingiva than in control gingiva. 25,26) Interestingly, a2b1 integrin acts as positive regulator of type I collagen and collagenase gene expression. 64) So, the decreased collagen and collagenase gene expression in drug-induced gingival overgrowth in rat may be due to the reduction of a2 integrin expression on fibroblasts.…”

“…Although the pathology of drug-induced gingival overgrowth is not definitively known, these disorders seem to be induced through the disruption of the homeostasis of collagen synthesis and degradation in gingival connective tissues. [23][24][25][26][27] In this review, we focused on excess collagen fibers, especially type I collagen, the most abundant protein in mammals, 28) in gingival connective tissue, and discussed the role of collagen phagocytosis of gingival fibroblasts for the induction of drug-induced gingival overgrowth.…”

Nifedipine and phenytoin induce matrix synthesis, but not proliferation, in intact human gingival connective tissue ex vivo

“…An imbalance in the production and degradation of type I collagen, the major ECM component in gingiva (Trojanowska et al 1998), has been shown to be prominent in DIGE (Kataoka et al 2001;Kanno et al 2008;McKleroy et al 2013). Human gingival fibroblasts (HGFs) isolated from fibrotic gingiva produce significantly greater levels of collagen, but additionally exhibit reduced collagenase activity compared to non-fibrotic HGFs (Tipton et al 1994).…”