Cartilage Oligomeric Matrix Protein–Derived Peptides Secreted by Cartilage Do Not Induce Responses Commonly Observed during Osteoarthritis

Sastre, E. Andrés; Zaucke, Frank; Witte-Bouma, Janneke; Osch, Gerjo J.V.M. van; Farrell, Eric

doi:10.1177/1947603520961170

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…The same group used COMP constructs based on the protein domain structure. However, these fragments were not able to modify the expression of genes involved in cartilage homeostasis [ 58 ]. The authors discussed that the activity of fragments generated by MMPs might be different.…”

Section: Discussionmentioning

confidence: 99%

“…This can now be investigated in more detail with fragments derived from our cleavage assay. A mass spectrometric analysis identified three COMP-derived peptides that are only present in OA cartilage [ 58 ]. It is unclear whether these peptides were generated by MMPs, but so far, no biologic activity on endothelial cells and synovial fibroblasts could be demonstrated and it remains to be determined if these peptides could influence chondrocytes [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

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Generation of Matrix Degradation Products Using an In Vitro MMP Cleavage Assay

Wagner

Rapp

Braun

et al. 2022

IJMS

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Matrix metalloproteinases (MMPs) play crucial roles in tissue homeostasis and pathologies by remodeling the extracellular matrix. Previous studies have demonstrated the biological activities of MMP-derived cleavage products. Furthermore, specific fragments can serve as biomarkers. Therefore, an in vitro cleavage assay to identify substrates and characterize cleavage patterns could provide important insight in disease-relevant mechanisms and the identification of novel biomarkers. In the pathogenesis of osteoarthritis (OA), MMP-2, -8, -9 and -13 are of vital importance. However, it is unclear which protease can cleave which matrix component. To address this question, we established an in vitro cleavage assay using recombinantly expressed MMPs and the two cartilage matrix components, COMP and thrombospondin-4. We found a time- and concentration-dependent degradation and an MMP-specific cleavage pattern for both proteins. Cleavage products can now be enriched and purified to investigate their biological activity. To verify the in vivo relevance, we compared the in vitro cleavage patterns with serum and synovial fluid from OA patients and could indeed detect fragments of similar size in the human samples. The cleavage assay can be adapted to other MMPs and substrates, making it a valuable tool for many research fields

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Generation of Matrix Degradation Products Using an In Vitro MMP Cleavage Assay

Wagner

Rapp

Braun

et al. 2022

IJMS

Self Cite

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“…However, deposition of this protein in tumor stroma has been observed in breast cancer with a more invasive phenotype, partly due to upregulation of MMP-9 and genes protecting cancer cells from endoplasmic reticulum stress [172]. Remarkably, three peptides derived from COMP do not have a role in the regulation of TGF-β1 signaling and angiogenesis [173]. In periampullary adenocarcinoma, cancer cells and the surrounding stroma exhibit high COMP levels.…”

Section: Glycoproteinsmentioning

confidence: 99%

Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators

Sorvina

Antoniou

Esmaeili

et al. 2023

Cancers

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The extracellular matrix (ECM) is the complex three-dimensional network of fibrous proteins and proteoglycans that constitutes an essential part of every tissue to provide support for normal tissue homeostasis. Tissue specificity of the ECM in its topology and structure supports unique biochemical and mechanical properties of each organ. Cancers, like normal tissues, require the ECM to maintain multiple processes governing tumor development, progression and spread. A large body of experimental and clinical evidence has now accumulated to demonstrate essential roles of numerous ECM components in all cancer types. Latest findings also suggest that multiple tumor types express, and use to their advantage, atypical ECM components that are not found in the cancer tissue of origin. However, the understanding of cancer-specific expression patterns of these ECM proteins and their exact roles in selected tumor types is still sketchy. In this review, we summarize the latest data on the aberrant expression of bone and cartilage ECM proteins in epithelial cancers and their specific functions in the pathogenesis of carcinomas and discuss future directions in exploring the utility of this selective group of ECM components as future drug targets.

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“…Very recently, the effect of smaller COMP-derived peptides that have been detected in the degenerated cartilage tissue of OA patients was studied in different in vitro assays. Here, COMP peptides turned out to be rather inert and did not affect the viability of osteo-chondroprogenitor cells, nor the tube formation capacity of endothelial cells nor the cytokine release in synovial explant cultures [ 82 ].…”

Section: The Role Of Proteases and Cytokines In Oamentioning

confidence: 99%

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

Grässel

Zaucke

Madry

2021

JCM

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Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% of the world’s population over 60 years of age suffers from symptomatic (painful, disabling) OA. The disease poses a tremendous economic burden on the health-care system and society for diagnosis, treatment, sick leave, rehabilitation, and early retirement. Most patients also experience sleep disturbances, reduced capability for exercising, lifting, and walking and are less capable of working, and maintaining an independent lifestyle. For patients, the major problem is disability, resulting from joint tissue destruction and pain. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Here, we elucidate novel concepts and hypotheses regarding disease progression and pathology, which are relevant for understanding underlying the molecular mechanisms as a prerequisite for future therapeutic approaches. Emphasis is placed on topographical modeling of the disease, the role of proteases and cytokines in OA, and the impact of the peripheral nervous system and its neuropeptides.

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Cartilage Oligomeric Matrix Protein–Derived Peptides Secreted by Cartilage Do Not Induce Responses Commonly Observed during Osteoarthritis

Cited by 4 publications

References 30 publications

Generation of Matrix Degradation Products Using an In Vitro MMP Cleavage Assay

Generation of Matrix Degradation Products Using an In Vitro MMP Cleavage Assay

Unusual Suspects: Bone and Cartilage ECM Proteins as Carcinoma Facilitators

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

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