Universität zu Köln

Seifer, P., Hay, E., Fleischhauer, L., Heilig, J., Bloch, W., Sonntag, S., Shmerling, D., Clausen-Schaumann, H., Aszodi, A., Niehoff, A., Cohen-Solal, M., Paulsson, M., Wagener, R. and Zaucke, F. (2021). The Matrilin-3 T298M mutation predisposes for post-traumatic osteoarthritis in a knock-in mouse model. Osteoarthritis Cartilage, 29 (1). S. 78 - 89. OXFORD: ELSEVIER SCI LTD. ISSN 1522-9653

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Abstract

Objective: The human matrilin-3 T303M (in mouse T298M) mutation has been proposed to predispose for osteoarthritis, but due to the lack of an appropriate animal model this hypothesis could not be tested. This study was carried out to identify pathogenic mechanisms in a transgenic mouse line by which the mutation might contribute to disease development. Methods: A mouse line carrying the T298M point mutation in the Matn3 locus was generated and features of skeletal development in ageing animals were characterized by immunohistology, micro computed tomography, transmission electron microscopy and atomic force microscopy. The effect of transgenic matrilin-3 was also studied after surgically induced osteoarthritis. Results: The matrilin-3 T298M mutation influences endochondral ossification and leads to larger cartilage collagen fibril diameters. This in turn leads to an increased compressive stiffness of the articular cartilage, which, upon challenge, aggravates osteoarthritis development. Conclusions: The mouse matrilin-3 T298M mutation causes a predisposition for post-traumatic osteoarthritis and the corresponding knock-in mouse line therefore represents a valid model for investigating the pathogenic mechanisms involved in osteoarthritis development. (C) 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Seifer, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hay, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fleischhauer, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heilig, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sonntag, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shmerling, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Clausen-Schaumann, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Aszodi, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehoff, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cohen-Solal, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaucke, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-595723
DOI:	10.1016/j.joca.2020.09.008
Journal or Publication Title:	Osteoarthritis Cartilage
Volume:	29
Number:	1
Page Range:	S. 78 - 89
Date:	2021
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1522-9653
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MATRIX PROTEIN; EXTRACELLULAR-MATRIX; A-DOMAIN; CARTILAGE; COLLAGEN; HAND; HYPERTROPHY; GROWTH; BONE; PROTEOGLYCAN Multiple languages Orthopedics; Rheumatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59572