SLPI Is Not Sleepy During Biophysical Force-induced Tooth Movement

Objectives: Despite considerable progresses in the identification of molecules that are implicated in orthodontic tooth movement (OTM), the mechanism to orchestrate concurrent and balanced events of OTM-induced alveolar bone (AB) resorption and formation remains largely unknown. We, for the first time, report secretory leukocyte peptidase inhibitor (SLPI) that is functionally regulated during OTM, in which the rat upper 1st molars were mesial moved.
Methods: Differential display-PCR revealed that SLPI level was differentially increased during OTM and this result was confirmed by real-time PCR and Western blotting. Increased immunoreactivity for SLPI was apparently detected in both compression and tension sides of the periodontal ligament (PDL), compared to the control. The in vitro force application to primary human PDL cells increased the SLPI expression in force-type- and -scale-independent manners.
Results: SLPI were downregulated by an inhibitor of adenyl cyclases that were upregulated by force application. Runx2, ALP and collagen1α were downregulated by SLPI-siRNA or –antibody, whereas upregulated by SLPI protein. SLPI itself was rarely localized in PDL cell nuclei but cytoplasm. SLPI did not induce mineralization, but augmented dexamethasone-induced mineralization via MAPK-dependent Runx2 upregulation which was demonstrated by ALP and arizalin red staining and increased ALP and collagen1α levels. Compression induced RANKL and MCSF expressions for osteoclastogenesis induction, whereas tension attenuated them in PDL cells. SLPI itself induced and furthermore augmented not tension- but compression-induced RANKL and MCSF.
Conclusions: These results may enlist SLPI as a new target molecule for therapeutic interventions in order to accelerate OTM, along with its antibacterial effects.