Degradation of cartilage aggrecan by collagenase‐3 (MMP‐13)

Fosang, Amanda J.; Knäuper, Vera; Murphy, Gillian; Neame, Peter J.

doi:10.1016/0014-5793(95)01539-6

Cited by 345 publications

(229 citation statements)

References 41 publications

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“…MMP-13 has a particular affinity for type II collagen and selectively enhances cleavage and denaturation of this type of collagen (43), and can also cleave aggrecan at specific sites (44). Interestingly, recent studies have also shown that retinoid-related signals strongly enhance the induction of MMP-13 in chondrocytic cells through the action of RAR-RXR heterodimers (45).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes

Ohno¹,

Im²,

Knudson³

et al. 2005

Arthritis & Rheumatism

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Objective. To document the activity profile of transcription factors following chondrocyte stimulation with hyaluronan (HA) hexasaccharides (HA 6 ) and to determine the expression of genes whose transcriptional activation is tightly associated with the transcription factors.Methods. Nuclear extracts from bovine articular chondrocytes treated with HA 6 were subjected to transcription factor protein-DNA array analysis. Electrophoretic mobility shift assay (EMSA) analyses were performed to confirm the results of protein-DNA array. The gene expressions of matrix metalloproteinase 3 (MMP-3), type II collagen, and cartilage oligomeric matrix protein (COMP) were examined by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), and protease activity was assessed by casein zymography.Results. In the protein-DNA array analysis, 12 transcription factors were up-regulated and 2 transcription factors were down-regulated in the chondrocytes treated with HA 6 . The transcription factors retinoic acid receptor (RAR), retinoid X receptor (RXR), and Sp-1 exhibited >2-fold increased activity by HA 6 treatment, as confirmed by EMSA. RT-PCR analysis showed that the expression levels of MMP-3, type II collagen, and COMP messenger RNA, which are tightly associated with the activation of RAR, RXR, or Sp-1, were upregulated by treatment with HA 6 . Addition of high molecular mass HA after HA 6 treatment resulted in abrogation of the MMP-3 induction. Conclusion.These results suggest that HA 6 increase the activity of multiple transcription factors in chondrocytes and signal the enhanced expression of key genes involved in cartilage-matrix remodeling and turnover. The data also demonstrate that high molecular mass HA has a potential to suppress the signaling activated by HA 6 .The glycosaminoglycan hyaluronan (HA) is a critical component of the extracellular matrix of articular cartilage. HA serves as a scaffold for the aggregation of cartilage proteoglycan (1) and, in this manner, forms a continuum of structure throughout the extracellular matrix. In addition, we have shown that HA facilitates the anchorage of these proteoglycan aggregates to the chondrocyte cell surface via its interaction with the membrane HA receptor CD44 (2-4). Thus, it is, in part, the interaction of chondrocytes directly with HA that constitutes the cell-matrix interaction that serves to regulate many aspects of chondrocyte metabolism (5). We have shown previously that one method of interference with the cell-matrix interactions of chondrocytes is through the use of excess small HA oligosaccharides, such as HA hexasaccharides (HA 6 ) (2,4,6). HA 6 compete with high molecular mass HA for CD44 binding; yet, they are too small in size to interfere with HA aggrecan or HA-link protein interactions (1,7,8).The consequences of this loss of cell-matrix interactions can be dramatic. In a previous study, we demonstrated that the addition of small HA oligosaccharides to human or bovine articular cartilage slices resulted in the apparent activation o...

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Section: Discussionmentioning

confidence: 99%

Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes

Ohno¹,

Im²,

Knudson³

et al. 2005

Arthritis & Rheumatism

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“…Both in human articular chondrocytes and spine discs, it appears that the activation of multiple MAPK pathways (ERK, JNK, and p38) is required for the expression of MMP-13 after stimulation with inflammatory cytokines and growth factors such as IL-1 and bFGF Muddasani et al, 2007;Li et al, 2008). Clinically, stringent regulation of MMP-13 within the chondrocytic cell signaling network, through a complex interplay of regulatory factors and elements, may be necessary given the potent degrading activity of MMP-13 against a wide spectrum of substrates in the ECM and its pivotal role when present in excess amounts in OA cartilage (Fosang et al, 1996;Mitchell et al, 1996).…”

Section: (C) Extracellular Signaling Mediated By Bfgfmentioning

confidence: 99%

“…Among the collagenases, collagenase-3 (MMP-13) has been found to play a significant role in the development of both OA and DDD (Billinghurst et al, 1997;Fernandes et al, 1998;Anderson et al, 2002;Le Maitre et al, 2004). In articular cartilage, MMP-13 is almost exclusively produced by chondrocytes and has a dual role in ECM *Correspondence to : Hee-Jeong Im, Ph.D., Cohn Research BD 516, 1735 W. Harrison, Chicago, IL 60612, 312-942-3091 (Tel), 312-942-3053 (fax), Email : Hee-Jeong_Sampen@rush.edu.destruction as it degrades bothaggrecan and collagen type II (Fosang et al, 1996;Mitchell et al, 1996;Reboul et al, 1996;Fernandes et al, 1998). In the IVD, MMP-13 expression increases with increasing severity of disc degeneration (Le Maitre et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis

Ellman

Muddasani

et al. 2008

Gene

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131

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“…In support of this contention, a strong correlation exists between specific cleavage of the aggrecan core protein at the Glu373-Ala374 bond and the release of aggrecan catabolites in response to IL-1: 6 fragments bearing this epitope are found in synovial fluids of OA patients. 7 In addition, cells from OA synovium produce more IL-1b than normal synovium, 8,9 and similarly, chondrocytes for OA cartilage secrete both IL-1a and IL-1b unlike normal chondrocytes. 10,11 It is also known that OA cartilage explants are more susceptible to the effects of IL-1 than similar explants from nonarthritic cartilage 12 and that this susceptibility is related to the expression of IL-1 receptor types 1 and 2 on chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

Extended haplotypes and linkage disequilibrium in the IL1R1–IL1A–IL1B–IL1RN gene cluster: association with knee osteoarthritis

et al. 2004

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The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P ¼ 0.00043; P c ¼ 0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P ¼ 0.0036; P c ¼ 0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P ¼ 0.02), and the protective IL1B-IL1RN haplotype conferred a fivefold reduced risk of OA (P ¼ 0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA.

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Degradation of cartilage aggrecan by collagenase‐3 (MMP‐13)

Cited by 345 publications

References 41 publications

Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes

Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes

Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis

Extended haplotypes and linkage disequilibrium in the IL1R1–IL1A–IL1B–IL1RN gene cluster: association with knee osteoarthritis

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