Appropriate Physical Therapies Prevent Degradation and Induce Repair in TMJDs

Objective: TMJDs, frequently inflammatory in nature, cause pain and degeneration of joints. Although there is no universal treatment, jaw exercises are invariably beneficial to inflamed TMJs. However, lack of mechanistic studies explaining the basis of these treatments has impeded their use to the fullest benefit for the patient. We hypothesize that mechanical signals generated during joint movement are antiinflammatory and initiate repair by upregulating wnt signaling involved in TMJ development. Methods: TMJ fibrochondrocytes, grown on flexible bottom plates, were subjected to cyclic tensile strain (CTS) (12%; 0.05Hz; Flexcell) with or without interleukin (IL)-1b. The transcriptional and functional activation of the NF-kB and Wnt signaling pathways was assessed by PCR, Western blots, and immunofluorescence. Results: The results revealed that CTS: (i) significantly suppresses IL-1b-induced upregulation of proinflammatory mediators including nitric oxide, prostaglandin-E2, cyclooxygenase-2, and matrix metalloproteases (MMPs); (ii) blocks IL-1b-mediated nuclear translocation of NF-kB via inhibition of I-kB phosphorylation and degradation; (iii) counteracts IL-1b-induced inhibition of constitutive wnt4, frizzled3, and GSK3b mRNA expression within 4h suggesting a role for wnt4 signaling; (iv) synergizes with IL-1b to downregulate LRP6, the canonical co-receptor for wnt4; and (v) abrogates IL-1b-induced b-catenin translation within 30 minutes. Conclusion: These findings are the first to demonstrate that appropriate signals generated by TMJ mobilization antagonize inflammation as well as upregulate fibrocartilage repair via cell proliferation and matrix synthesis. These signals, by inhibiting IL-1b-dependent transactivation of NF-kB lead to the inhibition of nitric oxide synthase-II, cyclooxygenase-2, and MMP transcription, preventing cartilage degradation and pain. Importantly, during inflammation, these signals also promote cartilage repair by upregulating signaling molecules in the canonical and non-canonical wnt pathways. Collectively, the data suggest that proper jaw exercises have the potential to treat/prevent the progression of inflammatory TMJDs as well as augment fibrocartilage regeneration and repair in patients with compromised TMJ function. NIH DE017269, DE015399.