Effect of low‐intensity pulsed ultrasound on the mineralization of force‐treated cementoblasts and orthodontically induced inflammatory root resorption via the Lamin A/C‐Yes associated protein axis

AIMS: Orthodontic treatment commonly results in orthodontically induced inflammatory root resorption (OIIRR). This condition arises from excessive orthodontic force, which triggerslocal inflammatory responses and impedes cementoblasts' mineralization capacity. Low-intensity pulsed ultrasound (LIPUS) shows potential in reducing OIIRR. However, the precise mechanisms through which LIPUS reduces OIIRR remain unclear. This study aimed to explore the effects and mechanisms of LIPUS on the mineralization of force-treated cementoblasts and its impact on OIIRR. METHODS: We established a rat OIIRR model and locally administered LIPUS stimulation for 7 and 14 days. We analyzed root resorption volume, osteoclast differentiation, and the expression of osteocalcin and yes-associated protein 1 (YAP1) using micro-computed tomography (micro-CT), hematoxylin and eosin, tartrate-resistant acid phosphatase, immunofluorescence and immunohistochemistry staining. In vitro, we applied compressive force and LIPUS to the immortalized mouse cementoblasts (OCCM30). We assessed mineralization using alkaline phosphatase (ALP) staining, alizarin red staining, real-time quantitative polymerase chain reaction, Western blotting and immunofluorescence staining. RESULTS: In rats, LIPUS reduced OIIRR, as evidenced by micro-CT analysis and histological staining. In vitro, LIPUS enhanced mineralization of force-treated OCCM30 cells, as indicated by ALP and alizarin red staining, upregulated mRNA expression of mineralization-related genes, and increased protein expression of mineralization markers. Mechanistically, LIPUS activated YAP1 signaling via the cytoskeleton-Lamin A/C pathway, supported by immunofluorescence and Western blot analysis. CONCLUSION: This study demonstrates that LIPUS promotes mineralization in force-treated cementoblasts and reduces OIIRR by activating YAP1 through the cytoskeletal-Lamin A/C signaling pathway. These findings provide fresh insights into how LIPUS benefits orthodontic treatment and suggest potential strategies for preventing and treating OIIRR.