Suppressing STAT3 activation impairs bone formation during maxillary expansion and relapse

Objectives: The mid-palatal expansion technique is commonly used to correct maxilla constriction in dental clinics. There is, however, a tendency for it to relapse, and the key molecules responsible for modulating bone formation remain elusive. Thus, this study aimed to investigate whether signal transducer and activator of transcription 3 (STAT3) activation contributes to osteoblast-mediated bone formation during palatal expansion and relapse. Methodology: Thirty male Wistar rats were randomly allocated into Ctrl (control), E (expansion only), and E+Stattic (expansion plus STAT3-inhibitor, Stattic) groups. Micro-computed tomography, micromorphology staining, and immunohistochemistry of the mid-palatal suture were performed on days 7 and 14. In vitro cyclic tensile stress (10% magnitude, 0.5 Hz frequency, and 24 h duration) was applied to rat primary osteoblasts and Stattic was administered for STAT3 inhibition. The role of STAT3 in mechanical loading-induced osteoblasts was confirmed by alkaline phosphatase (ALP), alizarin red staining, and western blots. Results: The E group manifested a greater arch width than the E+Stattic group after expansion, and the differences between the two groups remained significant after relapse. Active bone formation was detected in the E group with increased expression of ALP, COL-I, and Runx2, whereas the expression of osteogenesis-related factors was downregulated in the E+stattic group. After STAT3 inhibition, expansive force-induced bone resorption was attenuated, as demonstrated by TRAP staining. Furthermore, the administration of Stattic in vitro partially suppressed tensile stress-enhanced osteogenic markers in osteoblasts. Conclusions: Overall, STAT3 inactivation reduced osteoblast-mediated bone formation during palatal expansion and post-expansion relapse, suggesting that it may be a potential therapeutic target to treat force-induced bone formation.