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

This study aims to investigate the role of Plexin-B2 in tension-induced osteogenesis of periodontal ligament stem cells (PDLSCs) and its biomechanical mechanism.

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.

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.

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.