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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.

Authors+Show Affiliations

Dartmouth Medical School, Hanover, NH 03755, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -