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CpG ODN-induced matrix metalloproteinase-13 expression is mediated via activation of the ERK and NF-κB signalling pathways in odontoblast cells.
Int Endod J. 2013 Jul; 46(7):666-74.IE

Abstract

AIM

To investigate the effects of CpG ODN (CpG oligodeoxynucleotides) to model the action of bacterial challenge on pulpal matrix metalloproteinase-13 (MMP-13) expression and elucidate the associated intracellular signalling pathways.

METHODOLOGY

Real-time PCR was used to detect the effects of CpG ODN on MMP-13 mRNA expression levels in a murine odontoblast-lineage cell line (OLCs). The possible involvement of TLR9/MyD88, NF-κB or MAPK pathways involved in the CpG ODN-induced MMP-13 expression was examined by real-time PCR, transient transfection, luciferase activity assay and ELISA. Western blotting was performed to assay the phosphorylation of ERK at a range of time points.

RESULTS

MMP-13 was constitutively expressed in OLCs, and their exposure to CpG ODN significantly increased MMP-13 expression. Pre-treatment of OLCs with the inhibitory peptide MyD88, or chloroquine, attenuated the CpG ODN-induced expression of MMP-13. Treatment of the OLCs with CpG ODN increased NF-κB-luciferase activity. This activity was decreased by the over-expression of a nondegrading mutant of IκBα (IκBαSR), although enhanced by the over-expression of NF-κB p65. MMP-13 expression induced by CpG ODN was markedly suppressed by NF-κB inhibitors (pyrrolidine dithiocarbamate, PDTC), IκBα phosphorylation inhibitors (Bay 117082) or IκB protease inhibitor (L-1-tosylamido-2-phenylethyl chloromethyl ketone, TPCK). The inhibitor of ERK1/2, U0126, but not inhibitors of p38 MAPK and JNK, SB203580 and SP600125, decreased CpG ODN-mediated MMP-13 expression.

CONCLUSION

The CpG ODN-induced MMP-13 expression in OLCs is mediated through TLR9, NF-κB and the ERK pathway indicating that potentially the recognition of CpG ODN by TLR9 on odontoblasts may regulate the remodelling of injured dental pulp and hard tissues by inducing MMP-13 expression.

Authors+Show Affiliations

Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23331101

Citation

Zhang, J, et al. "CpG ODN-induced Matrix Metalloproteinase-13 Expression Is Mediated Via Activation of the ERK and NF-κB Signalling Pathways in Odontoblast Cells." International Endodontic Journal, vol. 46, no. 7, 2013, pp. 666-74.
Zhang J, Zhu QL, Huang P, et al. CpG ODN-induced matrix metalloproteinase-13 expression is mediated via activation of the ERK and NF-κB signalling pathways in odontoblast cells. Int Endod J. 2013;46(7):666-74.
Zhang, J., Zhu, Q. L., Huang, P., Yu, Q., Wang, Z. H., Cooper, P. R., Smith, A. J., & He, W. (2013). CpG ODN-induced matrix metalloproteinase-13 expression is mediated via activation of the ERK and NF-κB signalling pathways in odontoblast cells. International Endodontic Journal, 46(7), 666-74. https://doi.org/10.1111/iej.12043
Zhang J, et al. CpG ODN-induced Matrix Metalloproteinase-13 Expression Is Mediated Via Activation of the ERK and NF-κB Signalling Pathways in Odontoblast Cells. Int Endod J. 2013;46(7):666-74. PubMed PMID: 23331101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CpG ODN-induced matrix metalloproteinase-13 expression is mediated via activation of the ERK and NF-κB signalling pathways in odontoblast cells. AU - Zhang,J, AU - Zhu,Q L, AU - Huang,P, AU - Yu,Q, AU - Wang,Z H, AU - Cooper,P R, AU - Smith,A J, AU - He,W, Y1 - 2013/01/21/ PY - 2012/08/15/received PY - 2012/12/05/accepted PY - 2013/1/22/entrez PY - 2013/1/22/pubmed PY - 2014/5/21/medline SP - 666 EP - 74 JF - International endodontic journal JO - Int Endod J VL - 46 IS - 7 N2 - AIM: To investigate the effects of CpG ODN (CpG oligodeoxynucleotides) to model the action of bacterial challenge on pulpal matrix metalloproteinase-13 (MMP-13) expression and elucidate the associated intracellular signalling pathways. METHODOLOGY: Real-time PCR was used to detect the effects of CpG ODN on MMP-13 mRNA expression levels in a murine odontoblast-lineage cell line (OLCs). The possible involvement of TLR9/MyD88, NF-κB or MAPK pathways involved in the CpG ODN-induced MMP-13 expression was examined by real-time PCR, transient transfection, luciferase activity assay and ELISA. Western blotting was performed to assay the phosphorylation of ERK at a range of time points. RESULTS: MMP-13 was constitutively expressed in OLCs, and their exposure to CpG ODN significantly increased MMP-13 expression. Pre-treatment of OLCs with the inhibitory peptide MyD88, or chloroquine, attenuated the CpG ODN-induced expression of MMP-13. Treatment of the OLCs with CpG ODN increased NF-κB-luciferase activity. This activity was decreased by the over-expression of a nondegrading mutant of IκBα (IκBαSR), although enhanced by the over-expression of NF-κB p65. MMP-13 expression induced by CpG ODN was markedly suppressed by NF-κB inhibitors (pyrrolidine dithiocarbamate, PDTC), IκBα phosphorylation inhibitors (Bay 117082) or IκB protease inhibitor (L-1-tosylamido-2-phenylethyl chloromethyl ketone, TPCK). The inhibitor of ERK1/2, U0126, but not inhibitors of p38 MAPK and JNK, SB203580 and SP600125, decreased CpG ODN-mediated MMP-13 expression. CONCLUSION: The CpG ODN-induced MMP-13 expression in OLCs is mediated through TLR9, NF-κB and the ERK pathway indicating that potentially the recognition of CpG ODN by TLR9 on odontoblasts may regulate the remodelling of injured dental pulp and hard tissues by inducing MMP-13 expression. SN - 1365-2591 UR - https://www.unboundmedicine.com/medline/citation/23331101/CpG_ODN_induced_matrix_metalloproteinase_13_expression_is_mediated_via_activation_of_the_ERK_and_NF_κB_signalling_pathways_in_odontoblast_cells_ L2 - https://doi.org/10.1111/iej.12043 DB - PRIME DP - Unbound Medicine ER -