Lrp6/F-Actin Axis Drives Mechano-Osteogenesis In Pdlscs

The unclear function of Low-density lipoprotein receptor-related protein 6 (LRP6) in periodontal ligament stem cells (PDLSCs) mechanotransduction of osteogenic signals requires exploration to uncover its mechanistic impact on bone remodeling. LRP6 expression and its function in force-induced osteogenic differentiation of PDLSCs were analyzed via tension modeling and knockdown assays, with osteogenic capacity, proliferation, and cell morphology assessed by alkaline phosphatase (ALP) staining, ALP assays, qRT-PCR, western blot, and immunofluorescence. Visualization of cell morphological changes was achieved through crystalline violet staining, while F-actin alteration was confirmed using Western blotting, qRT-PCR, and phalloidin staining. YAP nucleoplasmic localization was evaluated through immunofluorescence and western blotting. YAP nucleoplasmic localization was evaluated through immunofluorescence and western blotting. Cytochalasin D was employed to investigate the impact of F-actin on osteogenic commitment and YAP switch behavior in mechanically induced PDLSCs. Mechanical loading robustly activated LRP6 in PDLSCs and PDL tissues, with LRP6 deficiency impairing force-induced osteogenic differentiation and proliferation. Intriguingly, LRP6 knockdown led to cytoskeletal disorganization by disrupting F-actin dynamics, which caused YAP to redistribute between the nucleus and cytoplasm and become inactive. Moreover, disrupted F-actin dynamics hindered osteogenic differentiation, proliferation, YAP nuclear translocation, and YAP activation in mechanically induced PDLSCs. We identified that LRP6 in PDLSCs acted as the mechanosensor regulating mechanical stress-inducible osteogenic commitment via the F-actin/YAP. Targeting LRP6 could offer a promising approach to managing alveolar bone remodeling and preventing orthodontic treatment relapse.