Regulation of osteoprotegerin gene expression in dental follicle cells.

Colony-stimulating factor-one (CSF-1) and parathyroid-hormone-related protein (PTHrP) down-regulate osteoprotegerin (OPG) gene expression in the dental follicle of the rat first mandibular molar. To examine this regulation at the signal transduction level, we treated cultured dental follicle cells with either phorbolmyristate acetate (PMA) or dibutyryl cyclic AMP (dbcAMP) to activate either protein kinase C (PKC) or protein kinase A (PKA). Our results demonstrate that PMA up-regulates OPG gene expression and down-regulates the expression of CSF-1 and the PTHrP receptor (PTHrP-R). Conversely, dbcAMP down-regulates OPG expression and up-regulates CSF-1 and PTHrP-R expression. Immunostaining shows that PMA also increases the steady-state levels of protein. Thus, treatment with agents that affect protein kinase activity also enhance the steady-state mRNA and protein levels of OPG, as well as decreasing the mRNA levels of CSF-1 and PTHrP-R. The PKC-alpha isoform may be critical in OPG regulation because PKC-alpha gene expression is enhanced by PMA and reduced by either CSF-1 or PTHrP.