LAUSR

AIMS Once the periodontal ligament (PDL) is damaged, its characteristic structure is difficult to regenerate. Copine7 (CPNE7) reportedly plays a functional role in the supporting periodontal attachment and PDL alignment. Herein, we demonstrated the regulatory mechanism of CPNE7 coordination with cytoskeleton re-organization and cementum attachment protein (CAP)-mediated attachment in PDL regeneration. METHODS The expression and localization of CPNE7, α-TUBULIN, ACTIN, and microtubule associated protein tau (TAU) were investigated in vitro. The effects of recombinant CPNE7 (rCPNE7) and CPNE7-derived peptides (CPNE7-DP) on the regulation of CAP were analyzed in vitro and PDL repair capacity was analyzed in vivo. RESULTS CPNE7 co-localized with F-ACTIN and induced α-TUBULIN expansion to the edge of human periodontal ligament cells (hPDLCs). The ACTIN and α-TUBULIN protein expressions were not elevated in rCPNE7-treated hPDLCs. rCPNE7 elevated the protein expression of TAU, which co-localized with F-ACTIN and α-TUBULIN. Replantation studies on mice revealed that well-attached and well-aligned PDLs were repaired in the rCPNE7 group. CPNE7-DP directly up-regulate the expression of CAP in vitro and promotes PDL regeneration in three-wall defect canine models in vivo. CONCLUSION Our findings suggest that CPNE7 functions in PDL repair by supporting PDL alignment through TAU-mediated cytoskeleton re-organization and direct regulation of CAP-mediated PDL attachments of PDLCs.