Mechanical activation of Piezo1 promotes osteoclastogenesis in orthodontic tooth movement

The initiation of bone remodeling by periodontal ligament cells (PDLCs) in response to force is pivotal for mediating orthodontic tooth movement (OTM). Piezo1 plays a pivotal role in the process of bone remodeling under mechanical stimulation. Our objective was to elucidate the role and mechanism of Piezo1 in force-treated PDLCs, and its influence on orthodontic bone remodeling.

Human PDLCs (hPDLCs) were isolated and treated with compressive force, along with either si-PIEZO1 or Yoda1. The expression of Piezo1 and the receptor activator of NF-kB ligand/osteoprotegerin (RANKL/OPG) ratio were assessed by quantitative real-time polymerase chain reaction (qPCR) and Western blots. Intracellular calcium ion influx was assessed with Fluo4-AM staining. The effect of force-treated hPDLCs on the osteoclastic differentiation of RAW264.7 cells was analyzed by tartrate-resistant acid phosphatase (TRAP) staining, qPCR and Western blots. After constructing the OTM model, rats were injected with GsMTx4 or Yoda1. OTM distance, osteoclast differentiation, and the expression of RANKL and phosphorylated-ERK1/2 was analyzed with micro-computed tomography, hematoxylin and eosin, TRAP, immunofluorescence and immunohistochemistry staining.

Compressive force-activated Piezo1 in hPDLCs mediated RANKL/OPG upregulation via ERK1/2 phosphorylation, thereby facilitating osteoclast differentiation. Yoda1 amplified this effect, while knocking down Piezo1 suppresses it in force-treated hPDLCs. In vivo, Yoda1 enhanced OTM and osteoclastogenesis in rats, while GsMTx4 inhibited these processes. The expression of phosphorylated-ERK1/2 in periodontal ligaments on the compressive side was enhanced by Yoda1 and attenuated by GsMTx4.

Compressive force-activated Piezo1 in PDLCs triggers the osteoclast differentiation and orthodontic bone remodeling via ERK1/2 signal pathway.