Regulation of CSF-1 and MCP-1 Gene Expression by BMP-2 in Dental Follicle Cells

The dental follicle sac is essential for tooth eruption. CSF-1 and MCP-1, released by dental follicle cells (DFC), stimulate the influx of monocytes into the follicle sac and enhance osteoclasts necessary for alveolar bone resorption. Objective: To determine the effect of BMP-2, synthesized by cells in the local microenvironment, on CSF-1 and MCP-1 gene expression in cultured DFC. Methods: The effect of BMP-2 on CSF-1 and MCP-1 mRNAs was determined by Northern blot analysis. Results: BMP-2 increased CSF-1 mRNA levels, reaching a peak effect by 8 hrs and subsiding to near-basal levels by 24 hrs. BMP-2 also increased MCP-1 mRNA, but with different time course kinetics. MCP-1 mRNA increased 3-fold in response to BMP-2 within 2 hrs, with rapid decline to basal levels at 12 hrs. To assess regulation at the transcriptional level, cells were pretreated with an RNA polymerase II inhibitor, DRB, which completely blocked CSF-1 and MCP-1 mRNA induction by BMP-2. The protein synthesis inhibitor, cyclohexamide, increased CSF-1 and MCP-1 mRNAs in both unstimulated and BMP-2-treated DFC, suggesting that these genes are also regulated posttranscriptionally by a labile protein. Conclusions: These findings suggest that BMP-2 indirectly regulates tooth eruption via CSF-1 and MCP-1. Transcriptional and posttranscriptional control of CSF-1 and MCP-1 expression may contribute to their relative abundance in the follicle sac. MCP-1 may be the earliest chemotactic signal for monocytes and subsequent release of CSF-1 may act synergistially with MCP-1 to enhance monocyte recruitment. Further understanding of the molecular mechanisms that regulate CSF-1 and MCP-1 may lead to more effective treatment for abnormal tooth eruption. Supported by grants AR42306 and VA Merit award (SLA).