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Article

Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis

1
Experimental Surgery and Regenerative Medicine (ExperiMed), Department of General, Trauma and Reconstructive Surgery, Munich University Hospital, Ludwig-Maximilians-University, 80336 Munich, Germany
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Center for Applied Tissue Engineering and Regenerative Medicine, Munich University of Applied Sciences, 80533 Munich, Germany
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Center for NanoScience, Ludwig-Maximilians University Munich, 80799 Munich, Germany
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Department of Molecular Medicine, Max Planck Institute for Biochemistry, 82152 Martinsried, Germany
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Center for Molecular Medicine, University of Cologne, 50923 Cologne, Germany
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Center for Biochemistry, Faculty of Medicine, University of Cologne, 50931 Cologne, Germany
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Cologne Center for Musculoskeletal Biomechanics, Faculty of Medicine and University Hospital of Cologne, 50931 Cologne, Germany
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Institute of Biomechanics and Orthopaedics, German Sport University Cologne, 50933 Cologne, Germany
*
Author to whom correspondence should be addressed.
Current address: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Current address: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 3K7, Canada.
Int. J. Mol. Sci. 2020, 21(2), 666; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020666
Received: 12 December 2019 / Revised: 10 January 2020 / Accepted: 15 January 2020 / Published: 19 January 2020
Matrilins (MATN1, MATN2, MATN3 and MATN4) are adaptor proteins of the cartilage extracellular matrix (ECM), which bridge the collagen II and proteoglycan networks. In humans, dominant-negative mutations in MATN3 lead to various forms of mild chondrodysplasias. However, single or double matrilin knockout mice generated previously in our laboratory do not show an overt skeletal phenotype, suggesting compensation among the matrilin family members. The aim of our study was to establish a mouse line, which lacks all four matrilins and analyze the consequence of matrilin deficiency on endochondral bone formation and cartilage function. Matn1-4−/− mice were viable and fertile, and showed a lumbosacral transition phenotype characterized by the sacralization of the sixth lumbar vertebra. The development of the appendicular skeleton, the structure of the growth plate, chondrocyte differentiation, proliferation, and survival were normal in mutant mice. Biochemical analysis of knee cartilage demonstrated moderate alterations in the extractability of the binding partners of matrilins in Matn1-4−/− mice. Atomic force microscopy (AFM) revealed comparable compressive stiffness but higher collagen fiber diameters in the growth plate cartilage of quadruple mutant compared to wild-type mice. Importantly, Matn1-4−/− mice developed more severe spontaneous osteoarthritis at the age of 18 months, which was accompanied by changes in the biomechanical properties of the articular cartilage. Interestingly, Matn4−/− mice also developed age-associated osteoarthritis suggesting a crucial role of MATN4 in maintaining the stability of the articular cartilage. Collectively, our data provide evidence that matrilins are important to protect articular cartilage from deterioration and are involved in the specification of the vertebral column. View Full-Text
Keywords: matrilin; cartilage; bone development; articular cartilage; osteoarthritis matrilin; cartilage; bone development; articular cartilage; osteoarthritis
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MDPI and ACS Style

Li, P.; Fleischhauer, L.; Nicolae, C.; Prein, C.; Farkas, Z.; Saller, M.M.; Prall, W.C.; Wagener, R.; Heilig, J.; Niehoff, A.; Clausen-Schaumann, H.; Alberton, P.; Aszodi, A. Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis. Int. J. Mol. Sci. 2020, 21, 666. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020666

AMA Style

Li P, Fleischhauer L, Nicolae C, Prein C, Farkas Z, Saller MM, Prall WC, Wagener R, Heilig J, Niehoff A, Clausen-Schaumann H, Alberton P, Aszodi A. Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis. International Journal of Molecular Sciences. 2020; 21(2):666. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020666

Chicago/Turabian Style

Li, Ping, Lutz Fleischhauer, Claudia Nicolae, Carina Prein, Zsuzsanna Farkas, Maximilian M. Saller, Wolf C. Prall, Raimund Wagener, Juliane Heilig, Anja Niehoff, Hauke Clausen-Schaumann, Paolo Alberton, and Attila Aszodi. 2020. "Mice Lacking the Matrilin Family of Extracellular Matrix Proteins Develop Mild Skeletal Abnormalities and Are Susceptible to Age-Associated Osteoarthritis" International Journal of Molecular Sciences 21, no. 2: 666. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020666

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