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Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3.
Arthritis Rheum 2000; 43(4):801-11AR

Abstract

OBJECTIVE

To examine the mechanism of interleukin-1 (IL-1)-induced collagenase 3 (matrix metalloproteinase 13 [MMP-13]) gene expression in cultured chondrocytes for the purpose of better understanding how the gene is induced in these cells, and how it contributes to cartilage degradation in osteoarthritis.

METHODS

The transcriptional and posttranscriptional responses of the MMP-13 gene to IL-1 were assessed first. Then, direct inhibitors of mitogen-activated protein kinase (MAPK) signaling pathways and a constitutive repressor of nuclear factor kappaB (NF-kappaB) were used to assess the role of each pathway in IL-1-mediated induction of MMP-13.

RESULTS

We found that IL-1 induction of MMP-13 requires p38 activity, c-Jun N-terminal kinase (JNK) activity and NF-kappaB translocation. These results suggest that both NF-kappaB and activator protein 1 transcription factors are necessary for IL-1 induction of MMP-13. We also compared the signaling pathways necessary for IL-1 to stimulate collagenase 1 (MMP-1) in articular chondrocytes and chondrosarcoma cells and found that IL-1 induction of MMP-1 requires different pathways from those required by MMP-13. In chondrosarcoma cells, MMP-1 induction depends on p38 and MEK (an MAPK kinase of the extracellular signal-regulated kinase pathway) and does not require JNK or NF-kappaB. In articular chondrocytes, inhibition of MEK had no effect, while inhibition of p38 gave variable results.

CONCLUSION

These studies demonstrate, for the first time, that p38, JNK, and NF-kappaB are required for IL-1 induction of MMP-13. The results also highlight the differential requirements for signaling pathways in the induction of MMP-1 and MMP-13. Additionally, they demonstrate that induction of MMP-1 by IL-1 in chondrocytic cells depends on unique combinations of signaling pathways that are cell type-specific.

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    Authors+Show Affiliations

    Mengshol JA
    Dartmouth Medical School, Hanover, NH 03755, USA.
    Vincenti MP
    No affiliation info available
    Coon CI
    No affiliation info available
    Barchowsky A
    No affiliation info available
    Brinckerhoff CE
    No affiliation info available

    MeSH

    ChondrocytesCollagenasesEnzyme InductionGene Expression RegulationHumansInterleukin-1JNK Mitogen-Activated Protein KinasesMAP Kinase Signaling SystemMatrix Metalloproteinase 1Matrix Metalloproteinase 13Mitogen-Activated Protein KinasesNF-kappa BTransfectionp38 Mitogen-Activated Protein Kinases

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    10765924

    Citation

    Mengshol, J A., et al. "Interleukin-1 Induction of Collagenase 3 (matrix Metalloproteinase 13) Gene Expression in Chondrocytes Requires P38, c-Jun N-terminal Kinase, and Nuclear Factor kappaB: Differential Regulation of Collagenase 1 and Collagenase 3." Arthritis and Rheumatism, vol. 43, no. 4, 2000, pp. 801-11.
    Mengshol JA, Vincenti MP, Coon CI, et al. Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum. 2000;43(4):801-11.
    Mengshol, J. A., Vincenti, M. P., Coon, C. I., Barchowsky, A., & Brinckerhoff, C. E. (2000). Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. Arthritis and Rheumatism, 43(4), pp. 801-11.
    Mengshol JA, et al. Interleukin-1 Induction of Collagenase 3 (matrix Metalloproteinase 13) Gene Expression in Chondrocytes Requires P38, c-Jun N-terminal Kinase, and Nuclear Factor kappaB: Differential Regulation of Collagenase 1 and Collagenase 3. Arthritis Rheum. 2000;43(4):801-11. PubMed PMID: 10765924.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. AU - Mengshol,J A, AU - Vincenti,M P, AU - Coon,C I, AU - Barchowsky,A, AU - Brinckerhoff,C E, PY - 2000/4/15/pubmed PY - 2000/5/20/medline PY - 2000/4/15/entrez SP - 801 EP - 11 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 43 IS - 4 N2 - OBJECTIVE: To examine the mechanism of interleukin-1 (IL-1)-induced collagenase 3 (matrix metalloproteinase 13 [MMP-13]) gene expression in cultured chondrocytes for the purpose of better understanding how the gene is induced in these cells, and how it contributes to cartilage degradation in osteoarthritis. METHODS: The transcriptional and posttranscriptional responses of the MMP-13 gene to IL-1 were assessed first. Then, direct inhibitors of mitogen-activated protein kinase (MAPK) signaling pathways and a constitutive repressor of nuclear factor kappaB (NF-kappaB) were used to assess the role of each pathway in IL-1-mediated induction of MMP-13. RESULTS: We found that IL-1 induction of MMP-13 requires p38 activity, c-Jun N-terminal kinase (JNK) activity and NF-kappaB translocation. These results suggest that both NF-kappaB and activator protein 1 transcription factors are necessary for IL-1 induction of MMP-13. We also compared the signaling pathways necessary for IL-1 to stimulate collagenase 1 (MMP-1) in articular chondrocytes and chondrosarcoma cells and found that IL-1 induction of MMP-1 requires different pathways from those required by MMP-13. In chondrosarcoma cells, MMP-1 induction depends on p38 and MEK (an MAPK kinase of the extracellular signal-regulated kinase pathway) and does not require JNK or NF-kappaB. In articular chondrocytes, inhibition of MEK had no effect, while inhibition of p38 gave variable results. CONCLUSION: These studies demonstrate, for the first time, that p38, JNK, and NF-kappaB are required for IL-1 induction of MMP-13. The results also highlight the differential requirements for signaling pathways in the induction of MMP-1 and MMP-13. Additionally, they demonstrate that induction of MMP-1 by IL-1 in chondrocytic cells depends on unique combinations of signaling pathways that are cell type-specific. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/10765924/Interleukin_1_induction_of_collagenase_3__matrix_metalloproteinase_13__gene_expression_in_chondrocytes_requires_p38_c_Jun_N_terminal_kinase_and_nuclear_factor_kappaB:_differential_regulation_of_collagenase_1_and_collagenase_3_ L2 - https://doi.org/10.1002/1529-0131(200004)43:4<801::AID-ANR10>3.0.CO;2-4 DB - PRIME DP - Unbound Medicine ER -
    Grapherence [↓160]

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