Universität zu Köln

Wagner, Niklas, Rapp, Anna E., Braun, Sebastian ORCID: 0000-0003-4175-8718, Ehnert, Markus, Imhof, Thomas, Koch, Manuel ORCID: 0000-0002-2962-7814, Jenei-Lanzl, Zsuzsa, Zaucke, Frank ORCID: 0000-0002-7680-9354 and Meurer, Andrea (2022). Generation of Matrix Degradation Products Using an In Vitro MMP Cleavage Assay. Int. J. Mol. Sci., 23 (11). BASEL: MDPI. ISSN 1422-0067

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wagner, Niklas UNSPECIFIED UNSPECIFIED UNSPECIFIED Rapp, Anna E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Sebastian UNSPECIFIED orcid.org/0000-0003-4175-8718 UNSPECIFIED Ehnert, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Imhof, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Jenei-Lanzl, Zsuzsa UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaucke, Frank UNSPECIFIED orcid.org/0000-0002-7680-9354 UNSPECIFIED Meurer, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-669531
DOI:	10.3390/ijms23116245
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	23
Number:	11
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SYNOVIAL-FLUID; EXTRACELLULAR-MATRIX; SPINAL SENSITIZATION; PROTEIN-DEGRADATION; TISSUE INHIBITORS; II COLLAGEN; CARTILAGE; METALLOPROTEINASES; FRAGMENTS; THROMBOSPONDIN-4 Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66953