Cartilage Chondrolysis by Fibronectin Fragments Is Associated with Release of Several Proteinases: Stromelysin Plays a Major Role in Chondrolysis

Xie, Dong-Lin; Hui, Francis; Meyers, R.; Homandberg, Gene A.

doi:10.1006/abbi.1994.1228

Cited by 118 publications

(113 citation statements)

References 0 publications

Supporting

Mentioning

104

Contrasting

Order By: Relevance

“…This finding is consistent with the previous observation that the NH 2 -terminal HBFN-f also induces MMP-3 when inducing cartilage matrix degradation (49). HBFN-f also caused a significant release of proMMP-13 into media during days 0-4 and 4-8, followed by a decrease in MMP-13 production during days 8-12.…”

supporting

confidence: 92%

“…However, the effects of the COOH-terminal FN fragment itself on MMP expression have not been studied. In bovine articular cartilage explant cultures, amino-terminal heparin-, aminoterminal gelatin-, and central cell-binding fragments of FN stimulate MMP-3 and gelatinase expressions (40,49). To our knowledge, FN fragments have not been previously investigated in relation to collagen cleavage and to MMP-13 induction.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1?mediated pathway

Yasuda¹,

Poole²

2002

Arthritis & Rheumatism

115

View full text Add to dashboard Cite

supporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

A fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1?mediated pathway

Yasuda¹,

Poole²

2002

Arthritis & Rheumatism

115

View full text Add to dashboard Cite

“…Fibronectin, an extracellular matrix protein, can undergo proteolysis, yielding fragments that bind to integrin receptors and initiate signaling pathways that regulate cell growth, migration, and survival. Injection of fibronectin fragments directly into the synovial cavity leads to proteoglycan depletion and the induction of matrix-degrading enzymes (12,13). This activity has been attributed to the activation of the focal adhesion-associated tyrosine kinase pathway (14,15).…”

mentioning

confidence: 99%

Characterization of metalloprotease cleavage products of human articular cartilage

Zhen¹,

Brittain²,

Laska³

et al. 2008

Arthritis & Rheumatism

140

130

View full text Add to dashboard Cite

Objective. To identify, characterize, and compare proteolysis peptide products generated by metalloprotease digests of human articular cartilage.Methods. Human articular cartilage was digested by the addition of exogenous metalloproteases, including matrix metalloproteinases 2, 3, 8, 9, 12, and 13 and aggrecanases ADAMTS-4 and ADAMTS-5. Proteolyzed peptide products were identified by proteomics methods using mass spectrometry.Results. Complete sequences of the peptides proteolyzed from human articular cartilage, including Nand C-termini and hydroxylated posttranslational modifications, were determined. A wide variety of peptides, originating from types I, II, and III collagen, biglycan, prolargin, fibromodulin, fibronectin, decorin, cartilage oligomeric matrix protein, cartilage intermediate-layer protein, megakaryocyte-stimulating factor, mimecan, aggrecan, and lumican, was analyzed following metalloprotease digestion. Release of peptides varied as a function of time, enzyme specificity, and abundance. Specific type II collagen peptide biomarkers, including those containing the three-quarter-length fragment cleavage site and those containing the domains for helical peptide of type II collagen and C-telopeptide of type II collagen, were observed after release by selected proteases.Conclusion. The use of intact cartilage instead of purified protein substrates in the assay allowed for the identification of novel potential substrates and cleavage sites for individual enzymes under more physiologically relevant conditions. Characterization of these cartilage matrix peptides may help in the development of pharmacodynamic biomarkers of cartilage degradation, and also may contribute to an understanding of the bioactive peptides important in chondrocyte signaling.Osteoarthritis (OA) and rheumatoid arthritis (RA) are typified by biologic changes in the articular cartilage that lead to cartilage degradation and joint space narrowing (1,2). Articular cartilage is composed of 2 primary matrix proteins, type II collagen and aggrecan, as well as a number of other matrix proteins that provide structural functions such as rigidity, flexibility, and compression damping. In addition, the cartilage matrix influences chondrocyte function through integrin receptor signaling, initiated via ligation of either intact matrix molecules or peptide fragments resulting from proteolytic activity (3).In arthritis, an imbalance of chondrocyte matrix synthesis and degradation leads to a net loss of matrix, and eventually to joint impairment. In OA, the excessive degradation is primarily due to the action of proteases released by chondrocytes, synovial cells, and macrophages (4). Numerous serine proteases and metalloproteases are overexpressed by these cells during the disease process, but specific metalloproteases, including the collagenase matrix metalloproteinase 13 (MMP-13) and the aggrecanase ADAMTS-5, are thought to be especially important for initiating and promoting cartilage matrix degradation in OA (5,6). MMP-13 cleaves type II collage...

show abstract

“…The various forms of fientiation [2]. Cathepsin D and thrombin digests of fibronectin bronectin are associated with different biological phenomena, added to cultures of articular-cartilage-tissue slices lead to such as establishment and maintenance of normal cell morpholgreatly elevated release of stromelysin 1 [3]. On the other hand, ogy, cell migration and wound healing [1,9].…”

mentioning

confidence: 99%

Expression of collagenase/gelatinase activity from basement‐membrane fibronectin

Boudjennah

Dalet-Fumeron

Pagano

1998

European Journal of Biochemistry

View full text Add to dashboard Cite

We have isolated the collagenase/gelatinase activity of fibronectin from a bovine lens capsule hydrolysate, using heparin-agarose, gelatin-agarose, immunopurification with polyclonal antibodies directed against bovine plasma fibronectin, and immunopurification with a monoclonal antibody directed against the extra-domain A of cellular fibronectin. The expression of collagenase/gelatinase activity by the purified fibronectin fragment was dependent on the incubation time at 37°C and the addition of gelatin to the purified sample. Under these conditions, the purified fibronectin fragment exhibited collagenase/ gelatinase activity, as measured by means of gelatin zymography and the intramolecularly quenched fluorogenic substrate of collagenases (7-methoxycoumarin-4-yl)-acetylprolylleucylglycylleucyl-[3-(2,4-dinitrophenyl)-L-2,3-diaminopropionyl]-alanylarginylamide. This activity was due to proteins of 47 kDa and 37 kDa, as indicated by the gelatin-zymography pattern. When the processing was analyzed, by means of SDS/PAGE under reducing conditions, purified starting material of 66 kDa and 55 kDa was observed, and molecular masses of 45, 30 and 27 kDa were found for the processed samples. Under these conditions, the processing was more significant when a substrate, i.e the fluorogenic peptide or gelatin, was added to the processing mixture. An inhibition-profile study showed a zinc-dependent collagenase activity. Using the 45-kDa chymotryptic fragment from human plasma fibronectin, which contains the collagen-binding site, the same results were obtained. These results allow us to define a thiol-dependent zinc metalloproteinase expressed after limited proteolysis of both basement membrane and plasma fibronectins. This proteinase contains a collagen-binding domain, a zinc-binding sequence, and a cysteine involved in catalysis. This enzyme is a member of the thimet family of zinc metalloproteinases.Keywords : cellular fibronectin ; collagenase; gelatinase; matrix metalloprotease; thimet peptidase.Fibronectin is a well-characterized glycoprotein of blood gene for plasma and cellular fibronectin has been found, both plasma and extracellular matrixes that presents a variety of func-fibronectin are strongly related at the structural level [7]. Thus, tional activities [1]. Recently, some biological activities associ-a similar proteolytic potential could be present in cellular fibroated with a conformational change and/or limited proteolysis nectin, and a study of the expression of these enzymatic properhave been described. For example, gelatinase A [matrix met-ties should be of interest. Nevertheless, from a single gene a alloproteinase (MMP)2], was able to release fibronectin frag-complex pattern of alternative mRNA splicing generates ments that stimulate cell migration and inhibit adipocyte differ-multiple fibronectin polypeptides [8]. The various forms of fientiation [2]. Cathepsin D and thrombin digests of fibronectin bronectin are associated with different biological phenomena, added to cultures of articular-cartilage-tis...

show abstract

Cartilage Chondrolysis by Fibronectin Fragments Is Associated with Release of Several Proteinases: Stromelysin Plays a Major Role in Chondrolysis

Cited by 118 publications

References 0 publications

A fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1?mediated pathway

A fibronectin fragment induces type II collagen degradation by collagenase through an interleukin-1?mediated pathway

Characterization of metalloprotease cleavage products of human articular cartilage

Expression of collagenase/gelatinase activity from basement‐membrane fibronectin

Contact Info

Product

Resources

About