Mir-27 Promotes Periodontal Regeneration via Osteogenesis/Angiogenesis

The interplay between osteogenesis and angiogenesis is an important prerequisite for successful bone regeneration as it provides capillary supply to the initial bone lamellae involved in skeletogenesis. The Wnt signaling pathway is one of the key signaling pathways promoting both osteogenesis and angiogenesis. In the present study, we evaluated the regenerative potential of microRNA-27 (miR-27) by delivering miR-27 mimic via lipid nanoparticles (LNPs) to enhance periodontal tissue repair through the targeted modulation of Secreted Frizzled-Related Protein 1 (SFRP1). Our study demonstrated that inflammatory conditions inhibit the expression and function of miR-27 in a periodontitis model. miR-27 treatment significantly upregulated key modulators of periodontal regeneration, including osteogenic markers (ALP, RUNX2, and COL1) and angiogenic factors (CD31, CD34, and VEGF). This treatment also resulted in increased alkaline phosphatase activity and enhanced mineral deposition, alongside improved spheroid sprouting and tube formation in Matrigel cultures. LNPs were applied to optimize miR-27 delivery for efficient transfection. In vivo implantation revealed that miR-27 accelerated extracellular matrix remodeling in subcutaneous implants, induced a 6-fold increase in neovascularization, and significantly enhanced periodontal tissue formation and bone regeneration, as evidenced by a 43.9% reduction in the distance between the alveolar bone ridge and the cementoenamel junction. Mechanistically, miR-27 promoted osteogenic and angiogenic responses by suppressing SFRP1, a known Wnt signaling inhibitor and validated target of miR-27, thereby activating the Wnt pathway. Together, these studies demonstrate that miR-27 mimic functioned as a bioactive molecule promoting periodontal tissue regeneration through angiogenesis coinciding with osteogenesis. Our study also suggests that the miR-27-LNPs/scaffold combination is an exciting novel agent for the treatment of periodontal disease.