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

Mengshol, John A.

doi:10.1093/nar/29.21.4361

Cited by 235 publications

(193 citation statements)

References 35 publications

Supporting

Mentioning

170

Contrasting

Unclassified

Order By: Relevance

“…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: 86%

“…Tardif et al reported that the Ϫ133-bp region of the promoter included high activity AP-1 and RUNX binding motifs, and that deletion to Ϫ39 bp diminished promoter activity to the basal level (34). 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).…”

Section: Discussionmentioning

confidence: 66%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 66%

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

View full text Add to dashboard Cite

show abstract

“…Transforming growth factor ␤ is shown to induce MMP13 gene expression but down-regulates MMP1 gene expression at the same time (34,35). Another recent study has shown that Runx-2, a tissuespecific constitutive transcription factor, is required for MMP13 expression in response to IL-1 (36). Also, MMP2 and MMP14 do not contain any AP-1 element, yet they are activated, like other MMP genes, by the same stimulus.…”

Section: Discussionmentioning

confidence: 99%

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis

Ray¹,

Kuroki²,

Cook³

et al. 2003

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To identify specific transcription factors that are activated in the cartilage tissue of osteoarthritis (OA) patients and are involved in the expression of matrix metalloproteinase 1 (MMP-1).Methods. DNase I footprint and electrophoretic mobility shift assays were performed to identify active elements of the MMP1 promoter and the transcription factors that interact with it. The relative abundance of the involved transcription factor in the cartilage was determined by immunohistochemical analysis. The role of serum amyloid A-activating factor 1 (SAF-1) in MMP-1 expression was assessed by transient transfection assay with plasmids containing either a functional or an antisense SAF-1 complementary DNA.Results. A novel promoter element was detected in the human MMP1 gene, and the inflammationresponsive transcription factor SAF-1 was found to interact with it. SAF-1 activity was detected in the chondrocytes of OA cartilage, where most of the cells stained positive for SAF-1. Overexpression of SAF-1 in OA chondrocytes increased the expression of the MMP1 promoter, and interference of endogenous SAF-1 activity by antisense SAF-1 messenger RNA inhibited interleukin-1-mediated MMP1 promoter activity.Conclusion. The results indicate that SAF-1 is involved in the regulation of MMP1 gene expression and it is highly abundant in the articular cartilage chondrocytes of OA patients. The data also demonstrate that control of SAF-1 activity can suppress induced expression of MMP-1. Conceivably, SAF-1 could be a potential therapeutic target to control the overexpression of MMP-1 associated with the pathogenesis of OA.

show abstract

“…Regulation of MMP13 gene expression by runt-related transcription factor 2 and AP-1 sites has been described in osteoblasts, hypertrophic chondrocytes, and stably transfected chondrocytic cell lines (47)(48)(49)(50). Moreover, recent studies have shown that estrogen receptor-a can regulate the expression of MMP-13, primarily through the AP-1 transcriptional regulatory site (51) in the HIG-82 cells.…”

Section: Figurementioning

confidence: 99%

Inhibition of Matrix Metalloproteinase-3 and -13 Synthesis Induced by IL-1β in Chondrocytes from Mice Lacking Microsomal Prostaglandin E Synthase-1

Gosset

Pigenet

Salvat

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Joint destruction in arthritis is in part due to the induction of matrix metalloproteinase (MMP) expression and their inhibitors, especially MMP-13 and -3, which directly degrade the cartilage matrix. Although IL-1β is considered as the main catabolic factor involved in MMP-13 and -3 expression, the role of PGE2 remains controversial. The goal of this study was to determine the role of PGE2 on MMP synthesis in articular chondrocytes using mice lacking microsomal PGE synthase-1 (mPGES-1), which catalyses the rate-limiting step of PGE2 synthesis. MMP-3 and MMP-13 mRNA and protein expressions were assessed by real-time RT-PCR, immunoblotting, and ELISA in primary cultures of articular chondrocytes from mice with genetic deletion of mPGES-1. IL-1β–induced PGE2 synthesis was dramatically reduced in mPGES-1−/− and mPGES-1+/− compared with mPGES-1+/+ chondrocytes. A total of 10 ng/ml IL-1β increased MMP-3 and MMP-13 mRNA, protein expression, and release in mPGES-1+/+ chondrocytes in a time-dependent manner. IL-1β–induced MMP-3 and MMP-13 mRNA expression, protein expression, and release decreased in mPGES-1−/− and mPGES-1+/− chondrocytes compared with mPGES-1+/+ chondrocytes from 8 up to 24 h. Otherwise, MMP inhibition was partially reversed by addition of 10 ng/ml PGE2 in mPGES-1−/− chondrocytes. Finally, in mPGES-1−/− chondrocytes treated by forskolin, MMP-3 protein expression was significantly decreased compared with wild-type, suggesting that PGE2 regulates MMP-3 expression via a signaling pathway dependent on cAMP. These results demonstrate that PGE2 plays a key role in the induction of MMP-3 and MMP-13 in an inflammatory context. Therefore, mPGES-1 could be considered as a critical target to counteract cartilage degradation in arthritis.

show abstract

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

Cited by 235 publications

References 35 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

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis

Inhibition of Matrix Metalloproteinase-3 and -13 Synthesis Induced by IL-1β in Chondrocytes from Mice Lacking Microsomal Prostaglandin E Synthase-1

Contact Info

Product

Resources

About