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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, John A. Mengshol, Matthew P. Vincenti, Constance E. Brinckerhoff

Dartmouth Scholarship

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-κB. 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 …