Mutual effect between neuropeptides and inflammatory cytokines in neurogenic SMSCs of human temporomandibular joint.

In temporomandibular disorders (TMD), pain takes place when neuropeptides stimulate synovial tissue to produce several cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, which activate neurons and glia of synovial membrane at the bilaminar regions of temporomandibular joint (TMJ). It has been reported that, after neurogenic differentiation, the synovial mesenchymal stem cells (SMSCs), deriving from TMJ, possess the same cytological features as the neuronal cells. This study examined the ability of substance P (SP) and calcitonin gene-related peptide (CGRP) to stimulate SMSCs and neurogenic SMSCs secreting inflammatory cytokines during TMD, evaluated the mutual effects of inflammatory cytokines and neuropeptides and tested the analgesic effect of hyaluronic acid (HA). The levels of IL-1β, IL-6 and TNF-α in SMSCs and neurogenic SMSCs in the presence of neuropeptides were measured by ELISA. SP and CGRP produced by SMSCs and neurogenic SMSCs were determined by RT-PCR and Western blotting. The results showed that the expression of SP and CGRP was significantly enhanced in the neurogenic SMSCs in response to IL-1β, IL-6 and TNF-α, and the effect was remarkably inhibited by HA. IL-1β, IL-6 and TNF-α, in return, could be enhanced in the neurogenic SMSCs upon stimulation by SP and CGRP. Neuropeptides and inflammatory cytokines might work mutually on the TMD pain. The HA-mediated analgesic effect may be implicated in the inhibition of SP and CGRP expression in neurogenic SMSCs.