Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes

Fichter, Michael; Körner, Ulrich; Schömburg, Jana; Jennings, Lawrence J.; Cole, Ada A.; Mollenhauer, Jürgen

doi:10.1002/jor.20001

Cited by 89 publications

(76 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The present investigation offers insights into the signaling events in articular chondrocytes mediated by collagen fragments and thus eventually to the contribution of cysteine proteases to cartilage degradation. Recently, some of us reported MMP-2, -3, -9, and -13 to be up-regulated by the treatment of cultured chondrocytes with collagen type II-derived peptides (20). Similar findings were also reported by others (48,49), and the results of the protease array shown here in Fig.…”

Section: Discussionsupporting

confidence: 91%

“…The inhibitor benzyloxycarbonyl-Leu-Gly nitrile (Z-LG-{CN}) was synthesized as previously described (33). A synthetic 29-mer peptide (Ntelo) was used, corresponding to the N-terminal telopeptide of human type II collagen (20). It was purchased from JPT Peptide Technologies (Berlin, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…According to literature data, about 1-3% of the total collagen dry mass in normal cartilage occurs as partially degraded collagen peptides (21,28,29) whereas this percentage is much larger in OA cartilage, namely up to 6% (28) or even 20% (29). Those peptides are not only diagnostic markers of cartilage degradation but may also initiate a cascade of matrix-degrading proteolytic activities (20,21). Fichter et al have shown levels of MMPs-2, -3, -9, and -13 mRNA, and protein to be elevated after stimulation by collagen degradation products and, in particular, by a sequence from the N-terminal telopeptide of collagen type II (Ntelo).…”

mentioning

confidence: 99%

“…Fichter et al have shown levels of MMPs-2, -3, -9, and -13 mRNA, and protein to be elevated after stimulation by collagen degradation products and, in particular, by a sequence from the N-terminal telopeptide of collagen type II (Ntelo). Thus, collagen peptides may contribute to the regulation of matrix turnover (20). It has been shown that pro-inflammatory cytokines like interleukin-1 (IL-1) and tumor necrosis factor ␣ (TNF␣) contribute substan-tially to the liberation of matrix-degrading enzymes from OA chondrocytes (30,31).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Cathepsins B, K, and L Are Regulated by a Defined Collagen Type II Peptide via Activation of Classical Protein Kinase C and p38 MAP Kinase in Articular Chondrocytes

Ruettger

Schueler

Mollenhauer

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Degradation of the extracellular matrix (ECM) is a prominent feature in osteoarthritis (OA), which is mainly because of the imbalance between anabolic and catabolic processes in chondrocytes resulting in cartilage and bone destruction. Various proteases act in concert to degrade matrix components, e.g. type II collagen, MMPs, ADAMTS, and cathepsins. Protease-generated collagen fragments may foster the destructive process. However, the signaling pathways associated with the action of collagen fragments on chondrocytes have not been clearly defined. The present data demonstrate that the N-terminal telopeptide of collagen type II enhances expression of cathepsins B, K, and L in articular chondrocytes at mRNA, protein, and activity levels, mediated at least in part through extracellular calcium. We also demonstrate that the induction is associated with the activation of protein kinase C and p38 MAP kinase.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Cathepsins B, K, and L Are Regulated by a Defined Collagen Type II Peptide via Activation of Classical Protein Kinase C and p38 MAP Kinase in Articular Chondrocytes

Ruettger

Schueler

Mollenhauer

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…A mixture of type II collagen fragments prepared by digestion of bovine type II collagen with bacterial collagenase causes increased release of glycosaminoglycans and collagen from cartilage explants (12). In addition, a 29-mer synthetic peptide of N-telopeptide of type II collagen modulates MMP expression in chondrocytes (6). A better understanding of the mechanisms involved in of p65 NF-κB (Fig.…”

Section: Discussionmentioning

confidence: 99%

Type II collagen peptide stimulates Akt leading to nuclear factor-κB activation: Its inhibition by hyaluronan

Yasuda

2014

Biomed. Res.

View full text Add to dashboard Cite

While nuclear factor (NF)-κB is a critical pathway for matrix metalloproteinase (MMP)-13 induction in chondrocytes, intracellular upstream events for NF-κB activation by the type II collagen peptide (CB12-II) with catabolic activities remain unclear. Hyaluronan (HA) of high molecular weight is clinically used for treatment of osteoarthritis (OA) by intra-articular injection. Although HA can suppress NF-κB activation by CB12-II, it is still obscure how HA affects intracellular upstream pathways leading to NF-κB up-regulation in response to CB12-II. Thus, this study was aimed to investigate the involvement of phosphoinositide-3-OH kinase (PI3K)/Akt in the inhibition of CB12-II-activated NF-κB pathway by HA in OA chondrocytes. In monolayer cultures, pretreatment with HA of 2700 kDa significantly inhibited MMP-13 production by CB12-II-stimulated chondrocytes. CB12-II activated Akt and NF-κB whereas HA down-regulated CB12-II-stimulated phosphorylation of Akt and NF-κB. Inhibition studies using LY294002 revealed the requirement of PI3K/Akt pathway for CB12-II-stimulated NF-κB activation in association with MMP-13 production. Pretreatment with anti-CD44 antibody reversed the inhibitory effects of HA on CB12-IIinduced production of MMP-13 and activation of Akt and NF-κB. Herein, we provided the first evidence that HA suppresses CB12-II-activated PI3K/Akt pathway leading to down-regulation of NF-κB with diminished MMP-13 production through interaction with CD44.Degradation products of cartilage matrix are recognized as important amplifiers in diseased joints like osteoarthritis (OA) because of the ability to stimulate cartilage destruction through catabolic activities (28). In OA cartilage, type II collagen is cleaved by collagenases, especially matrix metalloproteinase (MMP)-13 (4), resulting in denaturation of the triple helix of the collagen (10). Denaturation and degradation of type II collagen produce proteolytic fragments of type II collagen. Recent reports suggest that type II collagen fragments may alter the environment within cartilage matrix in OA to stimulate MMP induction (24). Our previous studies have demonstrated that a 24-mer synthetic peptide of type II collagen can stimulate type II collagen cleavage with MMP-13 induction in cartilage explant culture (25,35). This synthetic peptide named CB12-II is derived from the CB12 fragment which is generated with cyanogen bromide cleavage of type II collagen, and corresponds to the residues 195-218 of bovine type II collagen. MMP-13 induction by CB12-II has been found to require activation of catabolic intracellular signaling pathways such as p38 mitogen-activated protein kinase (32) and nuclear factor (NF)-κB (33). Nuclear factor (NF)-κB, which consists of p50 and p65 subunits, is critical in the regulation of many genes including cytokines, chemokines, and adhesion molecules. Activation of NF-κB is dependent on the phosphorylation and degradation of IκB, an endogenous inhibitor that binds to NF-κB in the cytoplasm (2). The released NF-κB then translocate...

show abstract

Scar‐Degrading Endothelial Cells as a Treatment for Advanced Liver Fibrosis

et al. 2022

View full text Add to dashboard Cite

matrix (ECM) in the liver is an important feature of liver cirrhosis. Recovery from liver cirrhosis is physiologically challenging, partially due to the ECM in scar tissue showing resistance to cell-mediated degradation by secreted matrix metalloproteinases (MMPs). Here, a cell-mediated ECM-degradation screening system (CEDSS) in vitro is constructed for high-throughput searching for cells with tremendous degradation ability. ECM-degrading liver sinusoidal endothelial cells (dLSECs) are screened using CEDSS, which exhibit 17 times the ability to degrade collagen when compared to other cells. The degradation ability of dLSECs is mediated by the upregulation of MMP9. In particular, mRNA expression of MMP9 shows an 833-fold increase in dLSECs compared to normal endothelial cells (nLSECs), and MMP9 is regulated by transcription factor c-Fos. In vivo, single intrasplenic injection of dLSECs alleviates advanced liver fibrosis in mice, while intraperitoneal administration of liver-targeting peptide-modified dLSECs shows enhanced fibrosis-targeting effects. Degradative human umbilical vein endothelial cells (dHUVECs) prove their enhanced potential of clinical translation. Together, these results highlight the potential of ECM-degrading endothelial cells in alleviating advanced liver fibrosis, thus providing remarkable insights in the development of ECM-targeting therapeutics.

show abstract

Collagen degradation products modulate matrix metalloproteinase expression in cultured articular chondrocytes

Cited by 89 publications

References 20 publications

Cathepsins B, K, and L Are Regulated by a Defined Collagen Type II Peptide via Activation of Classical Protein Kinase C and p38 MAP Kinase in Articular Chondrocytes

Cathepsins B, K, and L Are Regulated by a Defined Collagen Type II Peptide via Activation of Classical Protein Kinase C and p38 MAP Kinase in Articular Chondrocytes

Type II collagen peptide stimulates Akt leading to nuclear factor-κB activation: Its inhibition by hyaluronan

Scar‐Degrading Endothelial Cells as a Treatment for Advanced Liver Fibrosis

Contact Info

Product

Resources

About