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IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways.
Nucleic Acids Res. 2001 Nov 01; 29(21):4361-72.NA

Abstract

Osteoarthritic chondrocytes secrete matrix metalloproteinase-13 (MMP-13) in response to interleukin-1 (IL-1), causing digestion of type II collagen in cartilage. Using chondrocytic cells, we previously determined that IL-1 induced a strong MMP-13 transcriptional response that requires p38 MAPK, JNK and the transcription factor NF-kappaB. Now, we have studied the tissue-specific transcriptional regulation of MMP-13. Constitutive expression of the transcription factor Runx-2 correlated with the ability of a cell type to express MMP-13 and was required for IL-1 induction; moreover, Runx-2 enhanced IL-1 induction of MMP-13 transcription by synergizing with the p38 MAPK signaling pathway. Transiently transfected MMP-13 promoters were not IL-1 inducible. However, -405 bp of stably integrated promoter was sufficient for 5- to 6-fold IL-1 induction of reporter activity and this integrated reporter required the same p38 MAPK pathway as the endogenous gene. Finally, mutation of the proximal Runx binding site and the proximal AP-1 site blunted the transcriptional response to IL-1, and double mutation synergistically decreased reporter activity. In summary, our data suggest that the transcriptional MMP-13 response to IL-1 is controlled by the p38 pathway interacting at the MMP-13 promoter through the tissue-specific transcription factor Runx-2 and the ubiquitous AP-1 transcription factor.

Authors+Show Affiliations

Department of Medicine and Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11691923

Citation

Mengshol, J A., et al. "IL-1 Induces Collagenase-3 (MMP-13) Promoter Activity in Stably Transfected Chondrocytic Cells: Requirement for Runx-2 and Activation By P38 MAPK and JNK Pathways." Nucleic Acids Research, vol. 29, no. 21, 2001, pp. 4361-72.
Mengshol JA, Vincenti MP, Brinckerhoff CE. IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Res. 2001;29(21):4361-72.
Mengshol, J. A., Vincenti, M. P., & Brinckerhoff, C. E. (2001). IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Research, 29(21), 4361-72.
Mengshol JA, Vincenti MP, Brinckerhoff CE. IL-1 Induces Collagenase-3 (MMP-13) Promoter Activity in Stably Transfected Chondrocytic Cells: Requirement for Runx-2 and Activation By P38 MAPK and JNK Pathways. Nucleic Acids Res. 2001 Nov 1;29(21):4361-72. PubMed PMID: 11691923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. AU - Mengshol,J A, AU - Vincenti,M P, AU - Brinckerhoff,C E, PY - 2001/11/3/pubmed PY - 2002/1/5/medline PY - 2001/11/3/entrez SP - 4361 EP - 72 JF - Nucleic acids research JO - Nucleic Acids Res VL - 29 IS - 21 N2 - Osteoarthritic chondrocytes secrete matrix metalloproteinase-13 (MMP-13) in response to interleukin-1 (IL-1), causing digestion of type II collagen in cartilage. Using chondrocytic cells, we previously determined that IL-1 induced a strong MMP-13 transcriptional response that requires p38 MAPK, JNK and the transcription factor NF-kappaB. Now, we have studied the tissue-specific transcriptional regulation of MMP-13. Constitutive expression of the transcription factor Runx-2 correlated with the ability of a cell type to express MMP-13 and was required for IL-1 induction; moreover, Runx-2 enhanced IL-1 induction of MMP-13 transcription by synergizing with the p38 MAPK signaling pathway. Transiently transfected MMP-13 promoters were not IL-1 inducible. However, -405 bp of stably integrated promoter was sufficient for 5- to 6-fold IL-1 induction of reporter activity and this integrated reporter required the same p38 MAPK pathway as the endogenous gene. Finally, mutation of the proximal Runx binding site and the proximal AP-1 site blunted the transcriptional response to IL-1, and double mutation synergistically decreased reporter activity. In summary, our data suggest that the transcriptional MMP-13 response to IL-1 is controlled by the p38 pathway interacting at the MMP-13 promoter through the tissue-specific transcription factor Runx-2 and the ubiquitous AP-1 transcription factor. SN - 1362-4962 UR - https://www.unboundmedicine.com/medline/citation/11691923/IL_1_induces_collagenase_3__MMP_13__promoter_activity_in_stably_transfected_chondrocytic_cells:_requirement_for_Runx_2_and_activation_by_p38_MAPK_and_JNK_pathways_ L2 - https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/29.21.4361 DB - PRIME DP - Unbound Medicine ER -