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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

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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. / Lawrence, Elizabeth; Kague, Erika; Aggleton, Jessye; Harniman, Robert; Roddy, Karen; Hammond, Christina.

In: Philosophical Transactions B: Biological Sciences, Vol. 373, No. 1759, 20170335, 05.11.2018.

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@article{6c630f846e5246d4b212f87e91bdd8c0,
title = "The mechanical impact of loss of col11a2; mutant zebrafish show changes to joint shape and function which leads to early onset osteoarthritis",
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.",
keywords = "Zebrafish, BIOMECHANICS, development, Stickler syndrome, OSTEOARTHRITIS, material properties",
author = "Elizabeth Lawrence and Erika Kague and Jessye Aggleton and Robert Harniman and Karen Roddy and Christina Hammond",
year = "2018",
month = "11",
day = "5",
doi = "10.1098/rstb.2017.0335",
language = "English",
volume = "373",
journal = "Philosophical Transactions B: Biological Sciences",
issn = "0962-8436",
publisher = "The Royal Society",
number = "1759",

}

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TY - JOUR

T1 - The mechanical impact of loss of col11a2; mutant zebrafish show changes to joint shape and function which leads to early onset osteoarthritis

AU - Lawrence, Elizabeth

AU - Kague, Erika

AU - Aggleton, Jessye

AU - Harniman, Robert

AU - Roddy, Karen

AU - Hammond, Christina

PY - 2018/11/5

Y1 - 2018/11/5

N2 - 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.

AB - 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.

KW - Zebrafish

KW - BIOMECHANICS

KW - development

KW - Stickler syndrome

KW - OSTEOARTHRITIS

KW - material properties

U2 - 10.1098/rstb.2017.0335

DO - 10.1098/rstb.2017.0335

M3 - Article

VL - 373

JO - Philosophical Transactions B: Biological Sciences

T2 - Philosophical Transactions B: Biological Sciences

JF - Philosophical Transactions B: Biological Sciences

SN - 0962-8436

IS - 1759

M1 - 20170335

ER -