Regulation of gene expression of tumour necrosis factor-α by protein kinase C in the rat dental follicle

Tooth eruption requires alveolar bone resporption to form an eruption pathway. Recent studies suggest that tumour necrosis factor-α (TNF-α) may increase bone resorption by promoting the recruitment of mononuclear cells to the dental follicle to form osteoclasts. Although the major osteoclast burst is seen early postnatally in the rat (day 3), the second round of minor osteoclastogenesis is around postnatal day 10. We have previously reported that TNF-α is expressed in the dental follicle of newborn rats with maximum expression at day 9. Such expression is enhanced by IL-1α in cultured dental follicle cells. In this report, regulation of TNF-α expression by protein kinase C (PKC) was studied both in vitro and in vivo. Incubating dental follicle cells with phorbolmyristate acetate (PMA), a PKC activator, significantly up-regulated TNF-α gene expression in a dosage-dependent manner. A PKC specific inhibitor, Gö 6983, abolished this PMA effect on up-regulation of TNF-α, but had no effect on IL-1α induced expression. TNF-α expression was significantly greater after treatment with a combination of PMA and IL-1α than in treatments with PMA or IL-1α alone, suggesting a synergistic effect on enhancing TNF-α expression. These gene expression results were confirmed at the protein level by immunostaining for TNF-α in the dental follicle cells. In vivo, injection of PMA into postnatal rats also increased TNF-α expression. Thus, PKC up-regulates TNF-α expression in dental follicle cells, as does IL-1α. However, they appear to utilize different pathways to regulate TNF-α expression.