Importin-7 promotes tension-induced osteogenesis by regulating RUNX2 nuclear translocation during orthodontic tooth movement

Orthodontic tooth movement (OTM) is primarily driven by alveolar bone remodeling, wherein tension-induced osteogenesis plays a central role. Importin7 (IPO7) has been identified as a highly mechanoresponsive nuclear transport receptor (NTR). However, its role in regulating tension-induced osteogenesis during OTM and its underlying mechanism remains elusive. In the present study, cyclic tensile strain and a rat OTM model were used to investigate the role of IPO7. The results revealed that IPO7 was significantly expressed both in vitro and in vivo following exposure to mechanical stretch. Moreover, IPO7 knockdown inhibited tension-induced osteogenesis in BMSCs. Upon mechanical force stimulation, IPO7 translocated from the cytoplasm to the nucleus. Furthermore, immunoprecipitation (IP) coupled with mass spectrometry (MS) was performed and demonstrated that RUNX2 was one of the IPO7-interacting proteins related to osteogenesis. Although RUNX2 has been established to translocate to the nucleus to facilitate osteogenesis, whether it is IPO7 that regulate RUNX2 nuclear input during tension-induced osteogenesis remains to be determined. Then, the interaction between IPO7 and RUNX2 was further validated via co-immunoprecipitation (co-IP) and colocalization assays in BMSCs using immunofluorescence. Taken together, this study demonstrates that IPO7 promotes tension-induced osteogenesis by regulating the nucleoplasmic localization of RUNX2. Thus, targeting IPO7 may represent a prospective therapeutic strategy for enhancing alveolar bone remodeling and the efficacy of orthodontic treatment.

Alveolar bone remodeling; IPO7; Mechanotransduction; Nuclear translocation; RUNX2; Tooth movement.