Analysis of effect of IL-4 on mechanical loading-induced osteoclast formation and bone resorption

Objectives: Mechanical loading exerts important effects on the skeleton by controlling bone mass and strength. It also been reported that TNF-α plays an important role in mechanical loading-induced osteoclastogenesis and bone resorption. Interleukin (IL)-4 is a recognized immunomodulatory cytokine that regulates bone homeostasis. However, its influence on mechanical loading-induced osteoclast formation is still unknown. Thus, the purpose of this study was to analyze the effect and mechanism of IL-4 on mechanical loading-induced osteoclast formation and bone resorption.
Methods: Ten- to twelve-week-old male C57BL6/J mice were used in this study. The maxillary first molars of male mice were subjected to mesial force by A Ni-Ti coil spring. Varying doses of IL-4 from 0 to 1.5μg/day were injected locally adjacent to the first molar every other day. After 12 days of experimental tooth movement, the amounts of orthodontic movement and the number of tartrate-resistant acid phosphatase (TRAP)-positive cells along the loaded alveolar bone was calculated as osteoclasts, in histological sections. Furthermore, we investigated the mechanism of the effect of IL-4 on stromal cells and osteoclast precursors in TNF-α-mediated osteoclast formation in vitro by using western blotting and real time RT-PCR.
Results: The number of osteoclasts and bone resorption were significantly decreased in IL-4 treated mice. IL-4 inhibited TNF-α-induced RANKL expression in stromal cells. This event is dependent p38 inhibition.
Conclusions: IL-4 significantly suppressed the mechanical loading-induced osteoclast formation and bone resorption. These results suggest that IL-4 might be a useful adjunct to regulate the extent of mechanical loading-induced tooth movement.