Effect of intraoral mechanical stress application on the expression of a force-responsive prognostic marker associated with system disease progression

Objectives Malocclusion may be corrected nonsurgically by mechanical tooth movement. The plasma protein profiles of human subjects receiving the first phase of orthodontic treatment were examined to test the hypothesis that application of mechanical stresses to teeth induces systemic proteomic alterations. Methods Tandem mass tag-based liquid chromatography-mass spectrometry (LC–MS/MS) was used to examine systemic proteomic alterations in subjects undergoing controlled stress application (N = 10) and in volunteers not receiving treatment (N = 7) at 3 time intervals within 24 h. Proteins differentially expressed by the tooth movement group were functionally analyzed with “Gene Ontology” (GO) and “Search Tool to Retrieve Interacting Genes/proteins” (STRING) softwares. Enzyme-Linked Immunosorbent Assay and Western-blot were used to validate the in vivo protein alterations. An in vitro model consisting of human periodontal ligament cells (hPDLCs) under compression was used to validate the force-responsive characteristics of galectin-3 binding protein (LGALS3BP). Results Sixteen out of the 294 proteins identified by LC–MS/MS were differentially expressed in the plasma of subjects receiving controlled mechanical stresses for moving teeth. Those proteins were clustered in biological processes related to acute inflammatory response and vesicle-related transportation. Serotransferrin, fibronectin and LGALS3BP were processed for confirmation in vivo; LGALS3BP was significantly increased in the tooth movement group. In vitro secretion of LGALS3BP in PDLCs was force-responsive. Conclusions Regional application of mechanical stresses stimulates systemic proteomic changes. Because serum LGALS3BP is over-expressed in different systemic diseases, including cancer, further work is needed to examine how systemic up-regulation of LGALS3BP affects the progression of those diseases.