Inhibition of miR-508-5p Promotes Osteogenic-Angiogenic Coupling to Enhance Bone Formation.

Periodontal bone regeneration depends on the coordinated interplay between osteogenesis and angiogenesis; however, the molecular regulation underlying osteogenic-angiogenic coupling remains incompletely understood. Despite previous evidence that miR-508-5p downregulation enhances the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro, its role in regulating angiogenesis and bone formation in vivo remains unclear. In the present study, miR-508-5p was modulated using synthetic inhibitor and mimic oligonucleotides, and its effects on osteogenesis, angiogenesis, and osteogenic-angiogenic coupling were investigated by the use of alkaline phosphatase and alizarin red S staining, conditioned-medium assays, a chicken chorioallantoic membrane assay, and a nude mouse ectopic bone formation model. The responses to miR-508-5p inhibition differed by cell type: osteogenic differentiation increased in hPDLSCs, while human umbilical vein endothelial cells (HUVECs) showed greater proliferative, migratory, and tube-forming activity. Conditioned medium experiments further revealed that miR-508-5p inhibition enhanced the reciprocal paracrine effects between hPDLSCs and HUVECs, thereby promoting both osteogenic and angiogenic responses. In vivo, miR-508-5p inhibition enhanced bone-like tissue formation and collagen deposition, accompanied by the elevated expression of collagen type I alpha 1 chain, bone morphogenetic protein 2, and the angiogenic marker CD31. Taken together, the findings support a potential regulatory role for miR-508-5p in osteogenic-angiogenic coupling and indicate that this microRNA may warrant consideration as a candidate target in therapeutic strategies for periodontal bone regeneration.