Suppressing STAT3 activation impairs bone formation during maxillary expansion and relapse

Area of Science:

• Orthodontics and Dental Research
• Bone Biology and Osteogenesis
• Molecular Signaling Pathways

Background:

• Maxillary constriction is commonly treated with mid-palatal expansion, but relapse is frequent.
• The molecular mechanisms driving bone formation and resorption during palatal expansion and relapse are not fully understood.
• Signal transducer and activator of transcription 3 (STAT3) is a key signaling molecule implicated in cellular processes.

Purpose of the Study:

• To investigate the role of STAT3 activation in osteoblast-mediated bone formation during mid-palatal expansion and subsequent relapse.
• To determine if inhibiting STAT3 affects bone remodeling dynamics in response to orthodontic forces.

Main Methods:

• A rat model of palatal expansion was used, with groups receiving expansion only or expansion plus a STAT3 inhibitor (Stattic).
• Micro-computed tomography, histological staining (micromorphology, TRAP), and immunohistochemistry were employed to assess bone formation and resorption.
• Primary rat osteoblasts were subjected to mechanical stress in vitro with and without Stattic to evaluate STAT3's role in osteogenesis.

Main Results:

• Palatal expansion led to increased bone formation markers (ALP, COL-I, Runx2) in the absence of STAT3 inhibition.
• STAT3 inhibition significantly reduced bone formation during expansion and attenuated relapse.
• Inhibition of STAT3 in osteoblasts decreased the expression of osteogenic markers under mechanical loading and reduced bone resorption.

Conclusions:

• STAT3 activation plays a crucial role in osteoblast-mediated bone formation during palatal expansion and relapse.
• Inactivating STAT3 can mitigate excessive bone formation and potentially reduce relapse after orthodontic expansion.
• Targeting STAT3 signaling presents a potential therapeutic strategy for controlling bone remodeling in response to orthodontic forces.