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 language | English |
|---|---|
| Pages (from-to) | 1211-1223 |
| Number of pages | 13 |
| Journal | Journal of Cellular and Molecular Medicine |
| Volume | 23 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2019 |
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Keywords
- extracellular matrix
- integrin
- microenvironment
- migration
- periodontal ligament cells
ASJC Scopus subject areas
- Molecular Medicine
- Cell Biology
Cite this
Induction of migration of periodontal ligament cells by selective regulation of integrin subunits. / Kawamura, Mari; Yamamoto, Tadashi; Yamashiro, Keisuke; Kochi, Shinsuke; Yoshihara-Hirata, Chiaki; Ideguchi, Hidetaka; Aoyagi, Hiroaki; Omori, Kazuhiro; Takashiba, Shogo.
In: Journal of Cellular and Molecular Medicine, Vol. 23, No. 2, 01.02.2019, p. 1211-1223.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of migration of periodontal ligament cells by selective regulation of integrin subunits
AU - Kawamura, Mari
AU - Yamamoto, Tadashi
AU - Yamashiro, Keisuke
AU - Kochi, Shinsuke
AU - Yoshihara-Hirata, Chiaki
AU - Ideguchi, Hidetaka
AU - Aoyagi, Hiroaki
AU - Omori, Kazuhiro
AU - Takashiba, Shogo
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - extracellular matrix
KW - integrin
KW - microenvironment
KW - migration
KW - periodontal ligament cells
UR - http://www.scopus.com/inward/record.url?scp=85060590001&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060590001&partnerID=8YFLogxK
U2 - 10.1111/jcmm.14023
DO - 10.1111/jcmm.14023
M3 - Article
C2 - 30511442
AN - SCOPUS:85060590001
VL - 23
SP - 1211
EP - 1223
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
SN - 1582-1838
IS - 2
ER -