Induction of matrix metalloproteinase-13 gene expression by TNF-α is mediated by MAP kinases, AP-1, and NF-κB transcription factors in articular chondrocytes

Liacini, Abdelhamid; Sylvester, Judith; Li, Wen Qing; Huang, Wensheng; Dehnade, Faramaze; Ahmad, Mushtaq; Zafarullah, Muhammad

doi:10.1016/s0014-4827(03)00180-0

Cited by 288 publications

(235 citation statements)

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“…Mengshol et al reported similar results (35). Investigators in previous studies have concluded that signal transduction pathways modulating transcription factors such as AP-1, RUNX, and NF-B regulate expression of MMP-13 (11,12,(34)(35)(36)(37)(38)(39). We observed that double mutation of 2 C/EBP␤ binding motifs in this domain diminished promoter activity to basal levels and abolished the promoter's response to C/EBP␤ overexpression ( Figures 4C and D).…”

Section: Discussionsupporting

confidence: 84%

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CCAAT/ENHANCER binding protein β mediates expression of matrix metalloproteinase 13 in human articular chondrocytes in inflammatory arthritis

Hayashida¹,

Okazaki²,

Fukushi³

et al. 2009

Arthritis & Rheumatism

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Objective. To determine the function of CCAAT/ enhancer binding protein ␤ (C/EBP␤) in the expression of matrix metalloproteinase 13 (MMP-13) in chondrocytes in inflammatory arthritis.Methods. Cartilage obtained from patients with rheumatoid arthritis and osteoarthritis was immunostained for expression of C/EBP␤ or MMP-13. Interleukin-1␤-or tumor necrosis factor ␣ (TNF␣)-stimulated chondrocytes were subjected to Western blotting and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). MMP-13 promoter assays were conducted, and the C/EBP␤ response element was characterized by deletion and mutation analysis. C-28/I2 cells were treated with TNF␣ and subjected to chromatin immunoprecipitation (ChIP) assays. Finally, C/EBP␤-liver-enriched activator protein (LAP) was overexpressed in C-28/I2 cells or cartilage tissues, and MMP-13 expression was analyzed.Results. C/EBP␤ and MMP-13 expression was colocalized in chondrocytes in arthritic cartilage. MMP-13 promoter activity was stimulated by C/EBP␤ overexpression in a dose-dependent manner. Luciferase assays revealed that a -981-bp promoter had the greatest activity, while deletion to -936 bp strongly diminished promoter activity. Luciferase activity was repressed to basal levels by mutations in potential C/EBP binding sites. The stimulatory effects of C/EBP␤ overexpression were diminished by mutation. ChIP assays revealed that TNF␣ treatment enhanced the binding of C/EBP␤ to the MMP-13 promoter. When C/EBP␤-LAP was overexpressed in C-28/I2 cells, endogenous MMP-13 expression was stimulated up to 32-fold as detected by real-time RT-PCR. Furthermore, following adenoviral overexpression of C/EBP␤-LAP in organ culture of articular cartilage, stimulation of MMP-13 was also detected by immunohistochemistry. Conclusion. C/EBP␤ directly binds to the MMP-13 promoter region and stimulates the expression of MMP-13 in chondrocytes in inflammatory arthritis.Degeneration of articular cartilage is the principal process causing disability in patients with inflammatory arthritis, including those with rheumatoid arthritis (RA) (1,2) and osteoarthritis (OA) (3,4). Normally, maintenance of the cartilage extracellular matrix (ECM) is strictly regulated by the balance of anabolic and catabolic factors secreted by synovial cells or by chondrocytes themselves. Arthritic cartilage is characterized by excessive production of proteinases, such as matrix metalloproteinases (MMPs) and aggrecanases, and reduced synthesis of new matrix by chondrocytes, which disturbs the balance of anabolic and catabolic factors. Among the proteinases, MMP-13 cleaves a broad range of substrates, including fibrillar type II collagen and type II procollagen as well as gelatin, types I, III, IV, IX, X, and XIV collagen, tenascin, fibronectin, fibronectin fragments, and aggrecan (5-8). It has been reported that MMP-13 has the highest degradation activity for type II collagen (5,9). A recent study showed that up-regulated transgenic expression of MMP-13 in mouse articular cartilage resulted in pathologic chan...

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Section: Discussionsupporting

confidence: 84%

“…These pathways lead directly to the deterioration of cartilage matrix structures. IL-1␤ and TNF␣ treatment of chondrocytes induces many transcription factors related to inflammation, such as NF-B, IKK, activator protein 1 (AP-1) (11,12), early growth response 1 (13), and members of the CCAAT/enhancer binding protein (C/EBP) family (14).…”

mentioning

confidence: 99%

CCAAT/ENHANCER binding protein β mediates expression of matrix metalloproteinase 13 in human articular chondrocytes in inflammatory arthritis

Hayashida¹,

Okazaki²,

Fukushi³

et al. 2009

Arthritis & Rheumatism

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“…Furthermore, inhibition of NF-κB p65 pathways by PDTC, TPCK and Bay 11-7082 also reversed the leptin-induced increase of MMP-13 production. MMP-13 expression is also reported to be induced via NF-κB activation in chondrocytes (Liacini et al 2003;Ohno et al 2006). Since Morash et al (2000) reported that C6 glioma cells do not express long form of leptin receptor (ObRl), all the signal transduction observed in this study is due to the activation of short form of leptin receptor (ObRt).…”

Section: Discussionmentioning

confidence: 99%

“…Nuclear factor κB (NF-κB) is one of the transcription factors which can drive MMP-13 expression (Liacini et al 2003;Ohno et al 2006). Here we further examined whether NF-κB is involved in the action of leptin.…”

Section: Involvement Of P38 Mapk and Nf-κb Signaling Pathways In Leptmentioning

confidence: 99%

Leptin induces migration and invasion of glioma cells through MMP‐13 production

Yeh

Lee

et al. 2008

Glia

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Leptin, the product of the obses gene, plays an important role in the regulation of body weight by coordinating metabolism, feeding behavior, energy balance and neuroendocrine responses. However, central regulation of leptin gene expression is different from that in the adipocytes. In addition, leptin has been found in many tumor cell lines and has been shown to have mitogenic and angiogenic activity in a number of cell types. Glioma is the most common primary adult brain tumor with poor prognosis due to the spreading of tumor cell to the other regions of brain easily. Here we found that malignant C6 glioma cells expressed more leptin and leptin receptors than non-malignant astrocytes. Furthermore, it was found that exogenous application of leptin enhanced the migration and invasion of C6 glioma cells. In addition, we found that the expression of matrix metalloproteinase-13 (MMP-13) but not of MMP-2 and MMP-9 was increased in response to leptin stimulation. The leptin-induced increase of cell migration and invasion was antagonized by MMP-13 neutralizing antibody or silencing MMP-13. The up-regulation of MMP-13 induced by leptin was mainly through p38 MAP kinase and NF-κB pathway. In addition, migration-prone sublines demonstrate that cells with increasing migration ability had more expression of MMP-13 and leptin. Taken together, these results indicate that leptin enhanced migration and invasion of C6 glioma cells through the increase of 2

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“…7 Further, ERK pathway is involved in IL1-b and TNF-a induction of MMP-1, MMP-13, and ADAMTS-4 expression in chondrocytes. [8][9][10] In these studies, ERK1=2 pathway blockade prevents the production of proteinases induced by proinflammatory cytokine treatment.…”

Section: Introductionmentioning

confidence: 97%

ERK1/2 Activation Induced by Inflammatory Cytokines Compromises Effective Host Tissue Integration of Engineered Cartilage

Djouad

Rackwitz

Song

et al. 2009

Tissue Engineering Part A

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Induction of matrix metalloproteinase-13 gene expression by TNF-α is mediated by MAP kinases, AP-1, and NF-κB transcription factors in articular chondrocytes

Cited by 288 publications

References 41 publications

CCAAT/ENHANCER binding protein β mediates expression of matrix metalloproteinase 13 in human articular chondrocytes in inflammatory arthritis

CCAAT/ENHANCER binding protein β mediates expression of matrix metalloproteinase 13 in human articular chondrocytes in inflammatory arthritis

Leptin induces migration and invasion of glioma cells through MMP‐13 production

ERK1/2 Activation Induced by Inflammatory Cytokines Compromises Effective Host Tissue Integration of Engineered Cartilage

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