Objective: Orthodontic treatment is based upon an understanding of cellular responses to biomechanical forces. However, little is known about the manner in which cells respond to such forces, i.e, how is bone is remodeled in response to mechanical signals. Since inflammatory cytokines like IL-1b play a major role in bone remodeling, we hypothesized that mechanical signals may modulate PDL cell responses to IL-1b thus regulate bone resorption at compression sites and bone deposition at the tension sites. Methods: To test this, cultures of human PDL cells were grown on Bioflex plates, and subjected to equibiaxial cyclic tensile strain (TENS, 6 % to 15% elongation). Presence and/or absence of (rh)IL-1b for various time intervals was used as an inflammatory signal. The examination of the mRNA expression for multiple IL-1b-dependent proinflammatory genes was assessed by reverse transcriptase/polymerase chain reaction. Protein synthesis was assessed by Western blot analysis, and the nuclear translocation of NF-kB was examined by immunofluorescence. Results: Low magnitude TENS (6%) inhibited IL-1b-dependent induction of mRNA and proteins involved in catabolic actions of IL-1b, such as cyclooxygenase-2, matrix metalloprotease-1 (MMP-1), and MMP-3. Whereas, higher magnitudes of TENS (10 to 15%) did not suppress IL-1b actions. TENS (6%) also abrogated IL-1b-induced inhibition of tissue inhibitor of metalloprotease-II and collagen type I induction. Furthermore, examination of the signal transduction pathways of IL-1b showed that CTS inhibited IL-1b-induced nuclear factor (NF)-kB nuclear translocation. Conclusions: These findings are the first to show that intracellular signals generated by low magnitude of mechanical tensile strain interfere with one or more critical step(s) in the signal transduction cascade of rhIL-1b which inhibit nuclear translocation of NF-kB. These intracellular events may be critical in the bone deposition at the sites experiencing tension in response to applied mechanical forces during orthodontic tooth movement. Support NIH DE13799, AT00646.

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