Enhancement of gene expression in rat dental follicle cells by parathyroidhormone-related protein

Recent studies indicate that parathyroid hormone-related protein (PTHrP) is required for tooth eruption in mice. Localized in the stellate reticulum, PTHrP might exert a paracrine effect on cells of the adjacent dental follic le to initiate eruption. The presence of a follicle is needed for eruption and, at the cellular level, there is an influx of mononuclear cells in the follicle early postnatally in the first mandibular molar of the rat. In tur n, these mononuclear cells fuse to form osteoclasts, which erode the alveol ar bone to form an eruption pathway. At the molecular level, the dental fol licle cells of the rat molar maximally express the genes for monocyte chemo tactic protein-1 (MCP-1) and colony-stimulating factor-1 (CSF-1) at day 3 p ostnatally. Because day 3 also is the time of maximal influx of the mononuc lear cells into the follicle, MCP-I and CSF-1 could be involved in the recr uitment/maturation of these cells. To determine if PTHrP can modulate gene expression in the dental follicle, cultured follicle cells were immunostain ed to show the receptor for PTHrP. The gene expression of this receptor was enhanced by incubating the cells with interleukin-1 alpha (IL-1 alpha). Ne xt, the ability of PTHrP itself to enhance gene expression of either MCP-1 or CSF-1 in the dental follicle cells was determined by incubating the cell s with PTHrP in either a time- or concentration-course manner (1-15 h or 1- 100 ng/ml). By reverse transcription-polymerase chain reaction, it was demo nstrated that PTHrP enhanced MCP-1 expression in a concentration-dependent fashion, with 50 ng PTHrP/ml inducing maximal expression of either MCP-1 or CSF-1. In the time-dependent studies, PTHrP caused maximal expression with in 30 min for either MCP-1 or CSF-1. Immunoblotting revealed that PTHrP als o enhanced secretion of MCP-1 by the follicle cells. Thus, one of the actio ns of PTHrP in tooth eruption may be that it enhances MCP-1 and CSF-1 gene expression and secretion in the dental follicle. Moreover, IL-1 alpha may a ccentuate its action by enhancing the expression for the PTHrP receptor in the follicle cells. (C) 2000 Elsevier Science Ltd. All rights reserved.