CPNE7 regenerates periodontal ligament via TAU‐mediated alignment and cementum attachment protein‐mediated attachment

Abstract

Aim Once the periodontal ligament (PDL) is damaged, it is difficult to regenerate its characteristic structure. Copine7 (CPNE7) reportedly plays a functional role in supporting periodontal attachment and PDL alignment. Here we demonstrate the regulatory mechanism of CPNE7 coordination with cytoskeleton reorganization and cementum attachment protein (CAP)‐mediated attachment in PDL regeneration. Materials and 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 analysed in vitro, and PDL repair capacity was analysed in vivo. Results CPNE7 co‐localized with F‐ACTIN and induced α‐TUBULIN expansion to the edge of human PDL cells (hPDLCs). 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 promote PDL regeneration in three‐wall defect canine models in vivo. Conclusions Our findings suggest that CPNE7 helps in PDL repair by supporting PDL alignment through TAU‐mediated cytoskeleton reorganization and direct regulation of CAP‐mediated PDL attachments of PDLCs.

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“…CPNE7 is a pre-ameloblast-derived protein that has an important role in inducing odontoblast differentiation (63). Bai et al found that CPNE7 is beneficial to the recovery of damaged periodontal ligament by regulating tubulin-mediated cytoskeleton reorganization (64). HSF4 regulates lens development and prevents cataracts in a zebrafish model by activating p53 and its downstream genes (65).…”

Challenges of Periodontal Tissue Engineering: Increasing Biomimicry through 3D Printing and Controlled Dynamic Environment

“…PDLSCs transplanted into a periodontal lesion in a rat model generated typical PDL-like structures in vivo by forming Sharpey’s-fiber-like collagen bundles that are connected to cementum-like structures [ 20 ]. New insights into the molecular regulation of periodontal attachment have been brought by Bai S et al, who investigated the regulatory mechanism of copine 7 (CPNE7) and cementum attachment protein (CAP) in coordination with cytoskeleton arrangement [ 24 ]. Regenerating cementum is regarded as key to promoting new fibrous tissue attachment, preserving the PDL, and avoiding tooth ankylosis [ 25 ].…”