Orthodontic force regulates metalloproteinase-3 promoter in osteoblasts and transgenic mouse models.

Background/purpose: Previously we demonstrated up-regulation of matrix metalloproteinase-3 () in human osteoblasts under compression and in bony specimens of experimental orthodontic tooth movement (OTM). Here, we studied the temporal characteristics of compression stimulation in human and mouse osteoblast cell lines, and generated a transgenic mouse model for assessing the expression during OTM.

Materials And Methods: We investigated expressions in human and murine osteoblasts through RT-PCR and luciferase assay, after compressive force loading. Inhibitors were added to identify the possible mechanisms for signal transduction. A human promoter was isolated, cloned and transfected to generate a transgenic mouse with a green fluorescent protein reporter. OTM was then initiated to observe the location and time course of transcriptional regulation of signals.

Results: We found changes in the transcription of in response to mechanical force applied to both human and mouse osteoblast cell lines, suggesting that the response is positive across species. Cloned human promoter may cause the response of luciferase to 1% compression. Moreover, p38 inhibitor exerted a down-regulatory effect on promoter expression, although the inhibitory effect didn't reach a significant level. In the transgenic mouse OTM model, we again found increased expression of in response to mechanical force loading around the periodontal ligament.

Conclusion: Mechanical force can stimulate expression, possibly through the p38 MAPK pathway, with its strongest signal occurring at 24 h. The mechanical responsiveness in promoter regions can be observed in both humans and rodents in vitro and in vivo.