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The mechanical impact of loss of col11a2; mutant zebrafish show changes to joint shape and function which leads to early onset osteoarthritis

Research output: Contribution to journalArticle

Original languageEnglish
Article number20170335
Number of pages14
JournalPhilosophical Transactions B: Biological Sciences
Volume373
Issue number1759
Early online date24 Sep 2018
DOIs
DateAccepted/In press - 3 Jul 2018
DateE-pub ahead of print - 24 Sep 2018
DatePublished (current) - 5 Nov 2018

Abstract

Collagen is the major structural component of cartilage and mutations in the genes encoding Type XI collagen are associated with severe skeletal dysplasias (Fibrochondrogenesis and Stickler syndrome) and early onset osteoarthritis. The impact of the lack of Type XI collagen on cell behaviour and mechanical performance during skeleton development is unknown. We studied a zebrafish mutant for col11a2 and evaluated cartilage, bone development and mechanical properties to address this. We show that in col11a2 mutants Type II collagen is made but is prematurely degraded in maturing cartilage and ectopically expressed in the joint. These changes are correlated with increased stiffness of both bone and cartilage; quantified using Atomic Force Microscopy. In the mutants, the skeletal rudiment terminal region in the jaw joint are broader and the interzone smaller. These differences in shape and material properties impact on joint function and mechanical performance, which we modelled using Finite Element Analyses. Finally, we show that col11a2 heterozygous carriers reach adulthood but show signs of severe early onset osteoarthritis. Taken together our data demonstrate a key role for Type XI collagen in maintaining the properties of cartilage matrix; which when lost leads to alterations to cell behaviour that give rise to joint pathologies.

    Research areas

  • Zebrafish, BIOMECHANICS, development, Stickler syndrome, OSTEOARTHRITIS, material properties

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via the Royal Society at http://rstb.royalsocietypublishing.org/content/373/1759/20170335 . Please refer to any applicable terms of use of the publisher.

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