Copper stimulates human oral fibroblasts in vitro: a role in the pathogenesis of oral submucous fibrosis

Copper is implicated in the pathogenesis of several fibrotic disorders. Are ca nut has been shown to have a high copper content and areca chewing is as sociated with oral submucous fibrosis (OSF). The effects of copper on human oral fibroblasts were investigated in vitro. Human oral fibroblasts were i ncubated with copper chloride (CuCl2) at concentrations ranging from 0.01 m uM to 500 muM for 24 h, and in vitro cell proliferation was assayed by inco rporation of tritiated-thymidine; soluble and non-soluble collagen synthesi s was assayed using tritiated-proline. Addition of copper chloride at conce ntrations ranging from 0.1 muM to 50 muM increased the Collagen synthesis b y the oral fibroblasts compared with growth without copper (P < 0.05). The addition of copper chloride neither increased the synthesis of non-collagen ous proteins by the fibroblasts nor influenced their proliferation rate. We conclude that copper upregulates Collagen production in oral fibroblasts. This appears to be concentration dependent, with peak Collagen synthesis at 50 muM CuCl2. These in vitro results taken together with the recent findin gs of copper in oral biopsies from OSF subjects support the hypothesis that copper in areca nut acts as a mediator of OSF.