IL-6 regulates orthodontic tooth movement and pain

Takehito Ono, Naomi Toyama, Takashi Ono, Tomoki Nakashima

The 71st Annual Meeting of Japanese Association for Dental Research

Objectives
Orthodontic tooth movement (OTM) is accomplished by controlling the mechanical loading onto the alveolar bone, inducing its remodeling.  OTM often accompanies a side effect, periodontal pain.  Both tooth movement and pain are suggested to be regulated by inflammation after orthodontic intervention in the periodontal ligament (PDL) tissue.  However, underlying mechanisms are not well elucidated.  Thus, we addressed the mechanisms of the immune regulation over OTM and the related pain.
Methods
OTM mouse model was utilized.  To inhibit the cytokine signal specifically in the PDL, drugs were injected into the PDL space.  Effects of the inhibition were analyzed from the viewpoints of tooth movement, bone remodeling, pain behavior and gene expression.
Results
We found the interleukin-6 (IL-6) was highly expressed in the PDL by orthodontic intervention, with the activation of IL-6 signal (phosphorylation of STAT3) in the PDL.  In order to inhibit this signal specifically in the PDL, PDL injection technique was developed.  Using this technique, blockade of IL-6 was shown to decrease STAT3 activation and subsequent tooth movement.  IL-6 was found to increase the number of osteoclasts by suppressing apoptosis and increasing their responsiveness to macrophage colony–stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL).  Furthermore, IL-6 blockade was shown to alleviate orthodontic pain by reducing neuroinflammation in the trigeminal ganglion.
Conclusions
It was demonstrated that the IL-6 signal regulates tooth movement and pain during orthodontic treatment.  It was also indicated that local blockade of the IL-6 is a promising therapeutic option in orthodontic treatment, targeting both tooth movement and pain.