Interleukin-33 and superoxide dismutase 3 mediates co-achieved tooth movement acceleration and root protection

Achieving co-occurrence of tooth movement acceleration and root protection has been a fascinating challenge. This study investigated how interleukin-33 (IL-33)-superoxide dismutase 3 (SOD3) crosstalk affects the alveolar bone and cementum during orthodontic treatment.

The effects of IL-33-SOD3 signaling on the immortalized murine cementoblast cell line 30 cells, bone marrow stromal cells, and RAW 264.7 cells were evaluated. In vivo, the distance of orthodontic tooth movement and the volume of root resorption were quantified in mice treated with soluble suppression of tumorigenicity 2 (sST2, a decoy receptor for IL-33) and adenovirus-mediated sod3.

Endogenous SOD3 was found to enhance the osteogenic differentiation and mineralization of cementoblast-like cells, whereas IL-33-inhibited SOD3 expression and the SOD3-mediated promineralization effect on these cells. In bone marrow stromal cells, endogenous SOD3 promoted osteoblast differentiation and mineralization, although to a lesser extent than in the immortalized murine cementoblast cell line 30 cells, with a lack of effect of IL-33 on SOD3 expression. SOD3 attenuated osteoclastic activity in RAW 264.7 cells, to a lesser extent, compared with the IL-33-mediated suppression of osteoclastogenesis. Combined administration of sST2 and adenovirus-mediated sod3 gene transfer resulted in accelerated tooth movement while providing protection to the roots.

The SOD3 signaling cross-talked with IL-33 and differentially regulated cementoblast-like cells, osteoblast progenitors, and osteoclast precursor cells. Combined treatment of sST2 and sod3 gene transfer reorchestrated the IL-33-SOD3 signaling and led to accelerated bone remodeling coupled with reinforced root repair, achieving the co-occurrence of tooth movement acceleration and root protection in mice.