Effect of cyclic tensile force on the expression of bone morphogenetic protein 9 and interleukin 6 in human periodontal ligament cells

Abstract

Periodontium is a specialized tissue laying between tooth and surrounding bone. It functions as force cushion. In particular stimulation including mechanical force, periodontal ligament (PDL) cells which are mechanosensitive cells have the ability to secrete specific cytokines and proteins. PDL cells also have the potential to differentiate into osteoblast-like cells or fibroblast-like cells. PDL cells perceive combination of force in oral cavity in which major component is cyclic tensile force (CTF). CTF play an essential role in modulating PDL cells to maintain both hard and soft tissue integrity. Here, we demonstrated that CTF was able to stimulate the expression of osteoinductive genes including bone morphogenetic proteins (BMPs) by PDL cells. Among the BMPs, BMP9 is one of the most potent osteogenic BMPs. We showed that continuously applied CTF for only the first 6 hours stimulated the synthesis of BMP9 which enhanced the mineral deposition by 14 days. Stimulation of BMP9 expression depended on ATP and P2Y1 receptors by an increased level of intracellular Ca2+ through the phospholipase C (PLC) pathway. In addition, CTF also upregulated the expression of interleukin 6 (IL6) and MMPs. We demonstrated that CTF induced IL6 expression coincided with an increased matrix metaloproteinase 3 (MMP3) expression. A neutralizing IL6 antibody attenuated the CTF-increased MMP3 expression, whereas stimulating the cells with recombinant human IL6 increased MMP3 expression. Thus, CTF-induced IL6 increased the expression of MMP3. Collectively, our findings suggest an essential modulatory role of CTF in the homeostasis and regeneration of the periodontium.