Cyclic tensile force-upregulated IL6 increases MMP3 expression by human periodontal ligament cells

Cyclic tensile force (CTF) modulates physiological responses of periodontal ligament (PDL) cells. PDL cells are mechanosensitive and are able to maintain tissue homeostasis; a process mediated by the expression of particular cytokines including interleukin 6 (IL6). It is unknown whether CTF-induced IL6 regulates the expression of MMPs, enzymes needed for tissue remodeling.

Human PDL cells were subjected to 10% elongation strain of CTF at a frequency of 60 rpm continuously for 6 h. RNA and proteins were extracted and analyzed for IL6 and MMP expression by quantitative real-time PCR and ELISA, respectively. Using a neutralizing anti-IL6 antibody and addition of recombinant human IL6 at concentrations of 0.1, 1, 10 ng.mL^-1 were performed to clarify whether CTF-upregulated IL6 increased MMP expression. Inhibitors of intracellular signaling molecules were employed to reveal possible pathway(s) of IL6-induced MMP expression.

CTF-induced IL6 expression coincided with an increased MMP3 expression. A neutralizing anti-IL6 antibody attenuated the CTF-increased MMP3 expression, whereas stimulating the cells with recombinant human IL6 increased MMP3 expression. Both PI3K and MAPK pathways were essential in the IL6 induced expression of MMP3.

Our findings suggest a role of CTF in the modulation of expression of IL6 and MMP3 and thus in the regulation of homeostasis and remodeling of the periodontal ligament.