Plexin‐B2 Mediates Orthodontic Tension‐Induced Osteogenesis via the RhoA/F‐Actin/YAP Pathway

ABSTRACT Aims This study aims to investigate the role of Plexin‐B2 in tension‐induced osteogenesis of periodontal ligament stem cells (PDLSCs) and its biomechanical mechanism. Methods In vitro, cyclic tension simulated orthodontic forces to assess Plexin‐B2 expression in PDLSCs. We then knocked out Plexin‐B2 using lentivirus to explore its role in tension‐induced osteogenesis. In vivo, we used nickel‐titanium springs to establish orthodontic tooth movement (OTM) models in mice. Local periodontal Plexin‐B2 expression was knocked down using adeno‐associated viruses (AAVs) to study its influence on new bone formation under mechanical tension in OTM models. Molecular mechanisms were elucidated by manipulating Plexin‐B2 and RhoA expression, assessing related proteins, and observing F‐actin and Yes‐associated protein (YAP) through immunofluorescence. Results Plexin‐B2 expression in PDLSCs increased under cyclic tension. Decrease of Plexin‐B2 reduced the expression of osteogenic protein in PDLSCs and negatively affected new bone formation during OTM. RhoA expression and phosphorylation of ROCK2/LIMK2/Cofilin decreased in Plexin‐B2 knockout PDLSCs but were reversed by RhoA overexpression. The level of F‐actin decreased in Plexin‐B2 knockout PDLSCs but increased after RhoA rescue. Nuclear YAP was reduced in Plexin‐B2 knockout PDLSCs but increased after RhoA overexpression. Conclusions Plexin‐B2 is involved in tension‐induced osteogenesis. Mechanistically, the RhoA signaling pathway, the F‐actin arrangement, and the nuclear translocation of YAP are involved in the mechanotransduction of Plexin‐B2.