Mechanical Stress Regulates Alveolar Bone Remodeling Via Neat1-Induced Lymphangiogenesis

This study investigates the role of mechanical stress in alveolar bone remodeling through lymphangiogenesis, focusing on the involvement of periodontal ligament stem cells (PDLSCs) and the lncRNA NEAT1 in regulating the VEGFC/FLT4 signaling pathway. A unilateral tooth loss model in Sprague-Dawley rats was used to evaluate alveolar bone changes over eight weeks via microCT and immunofluorescence. In vitro, compression force was applied to PDLSCs, and exosomes secreted under stress were collected and applied to lymphatic endothelial cells (LECs) to assess lymphangiogenesis. A bilateral tooth loss rat model was also used, with exosome injections to compare bone remodeling effects. NEAT1 expression was validated, and its knockdown in LECs was performed, followed by RNA sequencing to analyze gene expression changes. Loss of occlusal force led to decreased bone density and reduced expression of bone and lymphatic markers. Exosomes from stressed PDLSCs enhanced LEC migration and tube formation. Injection of these exosomes promoted bone regeneration and increased lymphatic and bone markers. NEAT1 knockdown reduced lymphangiogenesis, and sequencing linked NEAT1 to the VEGF-VEGFR pathway. PDLSC-derived exosomes enriched with NEAT1 promote lymphangiogenesis and bone formation under mechanical stress, offering potential therapeutic targets for disuse osteoporosis of alveolar bone