Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

View ORCID ProfileElizabeth A Lawrence, View ORCID ProfileErika Kague, Jessye A Aggleton, Robert L Harniman, Karen A Roddy, View ORCID ProfileChrissy L Hammond
doi: https://doi.org/10.1101/302307
Elizabeth A Lawrence
1School of Physiology, Pharmacology and Neuroscience, University of Bristol BS8 1TD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Elizabeth A Lawrence
Erika Kague
1School of Physiology, Pharmacology and Neuroscience, University of Bristol BS8 1TD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Erika Kague
Jessye A Aggleton
2School of Anthropology and Archaeology, University of Bristol, BS8 1UU
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert L Harniman
3School of Chemistry, University of Bristol, BS8 1TS
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karen A Roddy
1School of Physiology, Pharmacology and Neuroscience, University of Bristol BS8 1TD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chrissy L Hammond
1School of Physiology, Pharmacology and Neuroscience, University of Bristol BS8 1TD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Chrissy L Hammond
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Collagen is the major structural component of cartilage and mutations in the genes encoding Type XI collagen are associated with severe skeletal dysplasias including Fibrochondrogenesis and Stickler syndrome, and with early onset osteoarthritis. Using a zebrafish mutant for col11a2 we test the impact of loss of Type XI collagen on cell behaviour and mechanical performance in the developing skeleton.

We show that in col11a2 mutants Type II collagen is made but is prematurely lost from maturing cartilage and ectopically expressed in the joint. Using Atomic Force Microscopy, we show that skeletal tissues (cartilage and bone) are stiffer in mutant zebrafish. We also observe wider joints with less defined interzones in mutants, which impacts on the function of the joint. Using Finite Element Analyses we model the mechanical performance of wild type and mutant joint shape and material properties; demonstrating that changing joint shape has a greater impact on the pattern of skeletal strain than material properties. Finally, we show that heterozygous carriers of the col11a2 mutation reach adulthood but are susceptible to severe, early onset, osteoarthritis. Taken together our data demonstrates 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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 17, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The mechanical impact of col11a2 loss on joints; col11a2 mutant zebrafish show changes to joint development and function, which leads to early onset osteoarthritis
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The mechanical impact of col11a2 loss on joints; col11a2 mutant zebrafish show changes to joint development and function, which leads to early onset osteoarthritis
Elizabeth A Lawrence, Erika Kague, Jessye A Aggleton, Robert L Harniman, Karen A Roddy, Chrissy L Hammond
bioRxiv 302307; doi: https://doi.org/10.1101/302307
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
The mechanical impact of col11a2 loss on joints; col11a2 mutant zebrafish show changes to joint development and function, which leads to early onset osteoarthritis
Elizabeth A Lawrence, Erika Kague, Jessye A Aggleton, Robert L Harniman, Karen A Roddy, Chrissy L Hammond
bioRxiv 302307; doi: https://doi.org/10.1101/302307

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Developmental Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4654)
  • Biochemistry (10299)
  • Bioengineering (7614)
  • Bioinformatics (26189)
  • Biophysics (13446)
  • Cancer Biology (10620)
  • Cell Biology (15333)
  • Clinical Trials (138)
  • Developmental Biology (8452)
  • Ecology (12754)
  • Epidemiology (2067)
  • Evolutionary Biology (16763)
  • Genetics (11356)
  • Genomics (15400)
  • Immunology (10548)
  • Microbiology (25041)
  • Molecular Biology (10152)
  • Neuroscience (54096)
  • Paleontology (398)
  • Pathology (1655)
  • Pharmacology and Toxicology (2877)
  • Physiology (4314)
  • Plant Biology (9196)
  • Scientific Communication and Education (1579)
  • Synthetic Biology (2541)
  • Systems Biology (6752)
  • Zoology (1452)