Bone Remodeling Optimization in Orthodontics: Harnessing Periodontal Ligament Cell-derived Exosomes and Anti-inflammatory Compounds.

Aim and background: Exosomes transport biological information between cells and can influence periodontal tissue remodeling. Particularly, the periodontal ligament cells (PDLCs) receive mechanical stimuli and transmit them via exosomes to osteoblasts and assist in tissue remodeling during the orthodontic treatment.

Materials and methods: This study uses computational methods to examine the effects of mechanical force-induced PDLC-transported exosomal micro RNA (miRNA) on osteoblast cells and to identify potential adjuvant therapies during orthodontic treatment.

Results: As a result of the investigation, 29 miRNAs were overrepresented in the PDLC-derived exosome, and when transported to osteoblasts, it regulates 3,768 mRNA targets, forming a vital gene interaction network. From the network, the crucial cluster was extracted, which plays a role in FoxO signaling, PI3K-Akt signaling, Ras signaling, and MAPK signaling pathways. Further, the cluster analysis with Cytohubba plug-in identified the basic leucine zipper and W2 domains 1 (BZW1) gene as a key target of miRNAs (hsa-let-7d-5p, hsa-miR-101-3p, and hsa-miR-15b-5p) in osteoblast cells. Molecular docking (MD) of 2,696 anti-inflammatory compounds against BZW1 indicates the least binding energy of -6.33 kcal/mol for C₂₁H₂₄N₄O₂ that effectively interacts with BZW1 protein. Further molecular mechanics-generalized born model and solvent accessibility analysis showed a free-binding energy of -34.56 kcal/mol for the C₂₁H₂₄N₄O₂-BZW1 complex. Finally, molecular dynamics simulation confirms stable confirmation of the C₂₁H₂₄N₄O₂-BZW1 complex.

Conclusion: Our study stipulates the molecular mechanisms that occurred in osteoblast cells upon mechanical stimuli in PDLC, which is critically useful to the development of adjuvant therapeutic molecules for the benefit of orthodontic treatment.

Clinical significance: The crucial mechanism by which exosomes deliver miRNAs to the osteoblast cells capable of inhibiting the significant genes/mRNAs could benefit orthodontic treatment. How to cite this article: Alhazmi AS. Bone Remodeling Optimization in Orthodontics: Harnessing Periodontal Ligament Cell-derived Exosomes and Anti-inflammatory Compounds. J Contemp Dent Pract 2025;26(1):77-85.