4.6 Article

The Matrilin-3 T298M mutation predisposes for post-traumatic osteoarthritis in a knock-in mouse model

Journal

OSTEOARTHRITIS AND CARTILAGE
Volume 29, Issue 1, Pages 78-88

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2020.09.008

Keywords

Matrilin-3; Polymorphism; Extracellular matrix; Osteoarthritis; Animal model

Funding

  1. German Research Foundation [FOR 2722-B1, FOR 2722-D1, Ni 1083/3e1, FOR 2722-D2]
  2. European Community [FP7/2007e2013 602300]

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The study found that the matrilin-3 T298M mutation affects endochondral ossification, resulting in larger cartilage collagen fibril diameters, which increases the compressive stiffness of articular cartilage and aggravates osteoarthritis development. This mutation predisposes mice to post-traumatic osteoarthritis and provides a valid model for investigating pathogenic mechanisms involved in osteoarthritis development.
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.

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