Signal transducer and activator of transcription 3 positively modulates orthodontic tooth movement speed and alveolar bone mass

Abstract

Objective To elucidate the role of signal transducer and activator of transcription 3 on orthodontic tooth movement, aiming at providing evidence for improving orthodontic bone modeling and remodeling. Methods Orthodontic tooth movement (OTM) models were established in 8-week-old Wistar rats, which were divided into 2 groups: the control group (tooth movement) and the test group (tooth movement with local injection of STAT3 inhibitor stattic). Rats were sacrificed on day 7 and 14. Micro-CT scanning was conducted to measure bone volume/tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and bone mineral density (BMD), and the amount of tooth movement of the specimens. The mouse preosteoblastic cell line MC3T3-e1 and mononuclear macrophagic leukemia cell line RAW264.7 were cocultured in Transwell® culture plates and divided into the control group (blank) and the test group (STAT3 inhibitor stattic was added). Alkaline phosphatase (ALP) staining and tartrate-resistant acid phosphatase (TRAP) staining were carried out to reveal osteoblastic and osteoclastic differentiation, respectively. qRT-PCR was performed to evaluate mRNA expression levels of the receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in the MC3T3-e1 cells. Results Compared with the control group, in the test group, the alveolar bone at the OTM site showed a significant decrease in the BV/TV, Tb.N, Tb.Th, and BMD indexes and a significant increase in Tb.Sp on day 14, while there was no significant difference in the above indexes between the two groups on day 7. The amount of tooth movement was significantly smaller in the test group on day 7 but showed no difference on day 14. ALP staining and TRAP staining revealed weakened osteoblastic and osteoclastic differentiation in the test group. qRT-PCR demonstrated the inhibitor inhibited the mRNA expression of RANKL and OPG and increased the mRNA ratio of RANKL/OPG in osteogenic precursor cells. Conclusion Suppression of STAT3 activation leads to inhibition of both osteoblastic and osteoclastic differentiation, resulting in lowered tooth movement and catabolic effects on alveolar bone. STAT3 may play an important role in orthodontic bone modeling and bone remodeling.

Keywords

• rats，
• tooth movement ，
• osteogenesis，
• osteoporosis，
• signal transducer and activator of transcription 3，
• stattic，
• osteoclast ，
• osteoblast，