Mechanical force orchestrates inflammatory and apoptosis-associated signaling in periodontal tissues during orthodontic tooth movement using complementary in vivo and in vitro models

Objectives To investigate the relationship between force-induced inflammation and intrinsic mitochondrial apoptosis-associated signaling in periodontal ligament (PDL) tissues during orthodontic tooth movement (OTM) using complementary in-vivo and in-vitro models. Materials and methods OTM was induced in six C57BL/6 mice using a nickel-titanium coil spring delivering approximately 30–35 g of force for 14 days. The contralateral side served as the untreated control. Micro-computed tomography (micro-CT) assessed tooth displacement. Histological and immunohistochemical analyses evaluated TNF-α, phosphorylated NF-κB, cytochrome c , and apoptotic protease activating factor 1 (APAF1). Human PDL fibroblasts were exposed to 2.0 g/cm 2 compressive force for 2, 4, 6, and 24 h. TNF-α, IL-6, and IL-8 mRNA expression was quantified using RT-PCR. Results Micro-CT revealed significantly greater inter-molar distance on the force-applied side than on the control side (0.2350 ± 0.0274 mm vs. 0.0750 ± 0.0187 mm; n = 6; paired p < 0.001). Immunohistochemistry showed increased TNF-α, phosphorylated NF-κB, cytochrome c , and APAF1 immunoreactivity in force-applied PDL tissues. In-vitro, TNF-α and IL-8 mRNA expression increased at 4, 6, and 24 h, while IL-6 expression was elevated at all time points, peaking at 4 h. Conclusions Orthodontic force induces inflammatory responses and alters mitochondrial apoptosis-associated signaling in periodontal tissues. These findings highlight potential interactions between inflammatory pathways and apoptosis-related molecular events during OTM. Further studies are required to establish whether these molecular changes result in apoptotic cell death.