4.6 Article

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

Journal

JOURNAL OF CLINICAL PERIODONTOLOGY
Volume 49, Issue 6, Pages 609-620

Publisher

WILEY
DOI: 10.1111/jcpe.13621

Keywords

CPNE7; cytoskeleton reorganization; PDL alignment; PDL attachment; TAU

Funding

  1. National Research Foundation [NRF-2018R1A5A2024418]
  2. Ministry of Education of the Republic of Korea

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The study demonstrates that CPNE7 plays a regulatory role in periodontal ligament (PDL) repair by supporting PDL alignment through TAU-mediated cytoskeleton reorganization and direct regulation of CAP-mediated PDL attachments of PDLCs.
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, alpha-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 alpha-TUBULIN expansion to the edge of human PDL cells (hPDLCs). ACTIN and alpha-TUBULIN protein expressions were not elevated in rCPNE7-treated hPDLCs. rCPNE7 elevated the protein expression of TAU, which co-localized with F-ACTIN and alpha-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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