Induction of migration of periodontal ligament cells by selective regulation of integrin subunits

Mari Kawamura, Tadashi Yamamoto, Keisuke Yamashiro, Shinsuke Kochi, Chiaki Yoshihara-Hirata, Hidetaka Ideguchi, Hiroaki Aoyagi, Kazuhiro Omori, Shogo Takashiba

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Abstract

The recruitment of tissue-resident stem cells is important for wound regeneration. Periodontal ligament cells (PDL cells) are heterogeneous cell populations with stemness features that migrate into wound sites to regenerate periodontal fibres and neighbouring hard tissues. Cell migration is regulated by the local microenvironment, coordinated by growth factors and the extracellular matrix (ECM). Integrin-mediated cell adhesion to the ECM provides essential signals for migration. We hypothesized that PDL cell migration could be enhanced by selective expression of integrins. The migration of primary cultured PDL cells was induced by platelet-derived growth factor-BB (PDGF-BB). The effects of blocking specific integrins on migration and ECM adhesion were investigated based on the integrin expression profiles observed during migration. Up-regulation of integrins α3, α5, and fibronectin was identified at distinct localizations in migrating PDL cells. Treatment with anti-integrin α5 antibodies inhibited PDL cell migration. Treatment with anti-integrin α3, α3-blocking peptide, and α3 siRNA significantly enhanced cell migration, comparable to treatment with PDGF-BB. Furthermore, integrin α3 inhibition preferentially enhanced adhesion to fibronectin via integrin α5. These findings indicate that PDL cell migration is reciprocally regulated by integrin α3-mediated inhibition and α5-mediated promotion. Thus, targeting integrin expression is a possible therapeutic strategy for periodontal regeneration.

Original languageEnglish
Pages (from-to)1211-1223
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

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Keywords

  • extracellular matrix
  • integrin
  • microenvironment
  • migration
  • periodontal ligament cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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