Mechanobiological Regulation of Alveolar Bone Remodeling: A Finite Element Study and Molecular Pathway Interpretation

<b>Background:</b> Mechanical loading is a fundamental regulator of bone remodelling; however, the mechanotransduction mechanisms governing alveolar bone adaptation under tensile-dominant orthodontic loading remain insufficiently defined. In particular, the molecular pathways associated with tension-driven cortical modelling in the periodontal ligament (PDL)-bone complex have not been systematically interpreted in the context of advanced biomechanical simulations. <b>Methods:</b> A nonlinear finite element model of the alveolar bone-PDL-tooth complex was developed using patient-specific CBCT data. Three loading configurations were analysed: (i) conventional orthodontic loading, (ii) loading combined with corticotomy alone, and (iii) a translation-dominant configuration generated by the Bone Protection System (BPS). Pressure distribution, displacement vectors, and stress polarity within the PDL and cortical plate were quantified across different bone density conditions. The mechanical outputs were subsequently interpreted in relation to established mechanotransductive molecular pathways involved in osteogenesis and angiogenesis. <b>Results:</b> Conventional loading generated compression-dominant stress fields within the marginal PDL, frequently exceeding physiological thresholds and producing moment-driven root displacement. Corticotomy alone reduced local stiffness but did not substantially alter stress polarity. The BPS configuration redirected loads toward a tensile-favourable mechanical environment characterised by reduced peak compressive pressures and parallel (translation-dominant) displacement vectors. The predicted tensile stress distribution is compatible with activation profiles of key mechanosensitive pathways, including integrin-FAK signalling, Wnt/β-catenin-mediated osteogenic differentiation and HIF-1α/VEGF-driven angiogenic coupling, suggesting a microenvironment that may be more conducive to cortical apposition than to resorption. <b>Conclusions:</b> This study presents a computational-molecular framework linking finite element-derived tensile stress patterns with osteogenic and angiogenic signalling pathways relevant to alveolar bone remodelling. The findings suggestthat controlled redirection of orthodontic loading toward tensile domains may shift the mechanical environment of the PDL-bone complex toward conditions associated with osteogenic than resorptive responses providing a mechanistic basis for tension-induced cortical modelling. This mechanobiological paradigm advances the understanding of load-guided alveolar bone adaptation at both the tissue and molecular levels.