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

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 ?3, ?5, and fibronectin was identified at distinct localizations in migrating PDL cells. Treatment with anti-integrin ?5 antibodies inhibited PDL cell migration. Treatment with anti-integrin ?3, ?3-blocking peptide, and ?3 siRNA significantly enhanced cell migration, comparable to treatment with PDGF-BB. Furthermore, integrin ?3 inhibition preferentially enhanced adhesion to fibronectin via integrin ?5. These findings indicate that PDL cell migration is reciprocally regulated by integrin ?3-mediated inhibition and ?5-mediated promotion. Thus, targeting integrin expression is a possible therapeutic strategy for periodontal regeneration.

SUBMITTER: Kawamura M

PROVIDER: S-EPMC6349235 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Kawamura Mari M Yamamoto Tadashi T Yamashiro Keisuke K Kochi Shinsuke S Yoshihara-Hirata Chiaki C Ideguchi Hidetaka H Aoyagi Hiroaki H Omori Kazuhiro K Takashiba Shogo S

Journal of cellular and molecular medicine 20181203 2

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 ...[more]

PMID: 30511442

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Project description:Initiation and progression of oral infectious diseases are associated with streptococcal species. Bacterial infection induces inflammatory responses together with reactive oxygen species (ROS), often causing cell death and tissue damage in the host. In the present study, we investigated the effects of oral streptococci on cytotoxicity and ROS production in human periodontal ligament (PDL) cells. Streptococcus gordonii showed cell cytotoxicity in a dose- and time-dependent manner. The cytotoxicity might be due to apoptosis since S. gordonii increased annexin V-positive cells, and the cytotoxicity was reduced by an apoptosis inhibitor, Z-VAD-FMK. Other oral streptococci such as Streptococcus mitis, Streptococcus sanguinis, and Streptococcus sobrinus also induced apoptosis, whereas Streptococcus mutans did not. All streptococci tested except S. mutans triggered ROS production in human PDL cells. Interestingly, however, streptococci-induced apoptosis appears to be ROS-independent, as the cell death induced by S. gordonii was not recovered by the ROS inhibitor, resveratrol or n-acetylcysteine. Instead, hydrogen peroxide (H2O2) appears to be important for the cytotoxic effects of streptococci since most oral streptococci except S. mutans generated H2O2, and the cytotoxicity was dramatically reduced by catalase. Furthermore, streptococcal lipoproteins are involved in cytotoxicity, as we observed that cytotoxicity induced by the lipoprotein-deficient S. gordonii mutant was less potent than that by the wild-type and was attenuated by anti-TLR2-neutralizing antibody. Indeed, lipoproteins purified from S. gordonii alone were sufficient to induce cytotoxicity. Notably, S. gordonii lipoproteins did not induce H2O2 or ROS but cooperatively induced cell death when co-treated with H2O2. Taken together, these results suggest that most oral streptococci except S. mutans efficiently induce damage to human PDL cells by inducing apoptotic cell death with bacterial H2O2 and lipoproteins, which might contribute to the progression of oral infectious diseases such as apical periodontitis.

Dataset Information

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

Publications

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

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