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Article ; Online: Strengths and opportunities in research into extracellular matrix ageing: A consultation with the ECMage research community.

Dalby, Matthew J / Pekovic-Vaughan, Vanja / Shanley, Daryl P / Swift, Joe / White, Lisa J / Canty-Laird, Elizabeth G

BioEssays : news and reviews in molecular, cellular and developmental biology

2024 Volume 46, Issue 5, Page(s) e2300223

Abstract: Ageing causes progressive decline in metabolic, behavioural, and physiological functions, leading to a reduced health span. The extracellular matrix (ECM) is the three-dimensional network of macromolecules that provides our tissues with structure and ... ...

Abstract	Ageing causes progressive decline in metabolic, behavioural, and physiological functions, leading to a reduced health span. The extracellular matrix (ECM) is the three-dimensional network of macromolecules that provides our tissues with structure and biomechanical resilience. Imbalance between damage and repair/regeneration causes the ECM to undergo structural deterioration with age, contributing to age-associated pathology. The ECM 'Ageing Across the Life Course' interdisciplinary research network (ECMage) was established to bring together researchers in the United Kingdom, and internationally, working on the emerging field of ECM ageing. Here we report on a consultation at a joint meeting of ECMage and the Medical Research Council / Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing, held in January 2023, in which delegates analysed the key questions and research opportunities in the field of ECM ageing. We examine fundamental biological questions, enabling technologies, systems of study and emerging in vitro and in silico models, alongside consideration of the broader challenges facing the field.
MeSH term(s)	Extracellular Matrix/metabolism ; Humans ; Aging ; Animals ; United Kingdom
Language	English
Publishing date	2024-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.202300223
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Article: Multimodal analysis of the differential effects of cyclic strain on collagen isoform composition, fibril architecture and biomechanics of tissue engineered tendon.

Janvier, Adam J / Pendleton, Emily G / Mortensen, Luke J / Green, Daniel C / Henstock, James R / Canty-Laird, Elizabeth G

Journal of tissue engineering

2022 Volume 13, Page(s) 20417314221130486

Abstract: Tendon is predominantly composed of aligned type I collagen, but additional isoforms are known to influence fibril architecture and maturation, which contribute to the tendon's overall biomechanical performance. The role of the less well-studied collagen ...

Abstract	Tendon is predominantly composed of aligned type I collagen, but additional isoforms are known to influence fibril architecture and maturation, which contribute to the tendon's overall biomechanical performance. The role of the less well-studied collagen isoforms on fibrillogenesis in tissue engineered tendons is currently unknown, and correlating their relative abundance with biomechanical changes in response to cyclic strain is a promising method for characterising optimised bioengineered tendon grafts. In this study, human mesenchymal stem cells (MSCs) were cultured in a fibrin scaffold with 3%, 5% or 10% cyclic strain at 0.5 Hz for 3 weeks, and a comprehensive multimodal analysis comprising qPCR, western blotting, histology, mechanical testing, fluorescent probe CLSM, TEM and label-free second-harmonic imaging was performed. Molecular data indicated complex transcriptional and translational regulation of collagen isoforms I, II, III, V XI, XII and XIV in response to cyclic strain. Isoforms (XII and XIV) associated with embryonic tenogenesis were deposited in the formation of neo-tendons from hMSCs, suggesting that these engineered tendons form through some recapitulation of a developmental pathway. Tendons cultured with 3% strain had the smallest median fibril diameter but highest resistance to stress, whilst at 10% strain tendons had the highest median fibril diameter and the highest rate of stress relaxation. Second harmonic generation exposed distinct structural arrangements of collagen fibres in each strain group. Fluorescent probe images correlated increasing cyclic strain with increased fibril alignment from 40% (static strain) to 61.5% alignment (10% cyclic strain). These results indicate that cyclic strain rates stimulate differential cell responses via complex regulation of collagen isoforms which influence the structural organisation of developing fibril architectures.
Language	English
Publishing date	2022-10-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2573915-3
ISSN	2041-7314
ISSN	2041-7314
DOI	10.1177/20417314221130486
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Article ; Online: Intrafascicular chondroid-like bodies in the ageing equine superficial digital flexor tendon comprise glycosaminoglycans and type II collagen.

Ali, Othman J / Ehrle, Anna / Comerford, Eithne J / Canty-Laird, Elizabeth G / Mead, Ashleigh / Clegg, Peter D / Maddox, Thomas W

Journal of orthopaedic research : official publication of the Orthopaedic Research Society

2021 Volume 39, Issue 12, Page(s) 2755–2766

Abstract: The superficial digital flexor tendon (SDFT) is considered functionally equivalent to the human Achilles tendon. Circular chondroid depositions scattered amongst the fascicles of the equine SDFT are rarely reported. The purpose of this study was the ... ...

Abstract	The superficial digital flexor tendon (SDFT) is considered functionally equivalent to the human Achilles tendon. Circular chondroid depositions scattered amongst the fascicles of the equine SDFT are rarely reported. The purpose of this study was the detailed characterization of intrafascicular chondroid-like bodies (ICBs) in the equine SDFT, and the assessment of the effect of ageing on the presence and distribution of these structures. Ultrahigh field magnetic resonance imaging (9.4T) series of SDFT samples of young (1-9 years) and aged (17-25 years) horses were obtained, and three-dimensional reconstruction of ICBs was performed. Morphological evaluation of the ICBs included histology, immunohistochemistry and transmission electron microscopy. The number, size, and position of ICBs was determined and compared between age groups. There was a significant difference (p = .008) in the ICB count between young and old horses with ICBs present in varying number (13-467; median = 47, mean = 132.6), size and distribution in the SDFT of aged horses only. There were significantly more ICBs in the tendon periphery when compared with the tendon core region (p = .010). Histological characterization identified distinctive cells associated with increased glycosaminoglycan and type II collagen extracellular matrix content. Ageing and repetitive strain frequently cause tendon micro-damage before the development of clinical tendinopathy. Documentation of the presence and distribution of ICBs is a first step towards improving our understanding of the impact of these structures on the viscoelastic properties, and ultimately their effect on the risk of age-related tendinopathy in energy-storing tendons.
MeSH term(s)	Aging ; Animals ; Collagen Type II ; Glycosaminoglycans ; Horses ; Tendinopathy/diagnostic imaging ; Tendinopathy/pathology ; Tendinopathy/veterinary ; Tendons/pathology
Chemical Substances	Collagen Type II ; Glycosaminoglycans
Language	English
Publishing date	2021-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605542-4
ISSN	1554-527X ; 0736-0266
ISSN (online)	1554-527X
ISSN	0736-0266
DOI	10.1002/jor.25002
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Article ; Online: Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice.

Lee, Katie J / Rambault, Lisa / Bou-Gharios, George / Clegg, Peter D / Akhtar, Riaz / Czanner, Gabriela / van 't Hof, Rob / Canty-Laird, Elizabeth G

Disease models & mechanisms

2022 Volume 15, Issue 9

Abstract: The osteogenesis imperfecta murine (oim) model with solely homotrimeric (α1)3 type I collagen, owing to a dysfunctional α2(I) collagen chain, has a brittle bone phenotype, implying that the (α1)2(α2)1 heterotrimer is required for physiological bone ... ...

Abstract	The osteogenesis imperfecta murine (oim) model with solely homotrimeric (α1)3 type I collagen, owing to a dysfunctional α2(I) collagen chain, has a brittle bone phenotype, implying that the (α1)2(α2)1 heterotrimer is required for physiological bone function. Here, we comprehensively show, for the first time, that mice lacking the α2(I) chain do not have impaired bone biomechanical or structural properties, unlike oim homozygous mice. However, Mendelian inheritance was affected in male mice of both lines, and male mice null for the α2(I) chain exhibited age-related loss of condition. Compound heterozygotes were generated to test whether gene dosage was responsible for the less-severe phenotype of oim heterozygotes, after allelic discrimination showed that the oim mutant allele was not downregulated in heterozygotes. Compound heterozygotes had impaired bone structural properties compared to those of oim heterozygotes, albeit to a lesser extent than those of oim homozygotes. Hence, the presence of heterotrimeric type I collagen in oim heterozygotes alleviates the effect of the oim mutant allele, but a genetic interaction between homotrimeric type I collagen and the oim mutant allele leads to bone fragility.
MeSH term(s)	Animals ; Collagen/genetics ; Collagen Type I/genetics ; Disease Models, Animal ; Homozygote ; Male ; Mice ; Mice, Mutant Strains ; Osteogenesis Imperfecta/genetics
Chemical Substances	Collagen Type I ; Collagen (9007-34-5)
Language	English
Publishing date	2022-09-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.049428
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Article ; Online: Identification and Characterization of Canine Ligament Progenitor Cells and Their Extracellular Matrix Niche.

Lee, Katie J / Comerford, Eithne J / Simpson, Deborah M / Clegg, Peter D / Canty-Laird, Elizabeth G

Journal of proteome research

2019 Volume 18, Issue 3, Page(s) 1328–1339

Abstract: Ligaments are prone to injury and degeneration in humans and animals, however the healing potential of ligament is poor and current treatment options ineffective. Stem cell-based therapies hold potential for treatment of ligament injuries. This study ... ...

Abstract	Ligaments are prone to injury and degeneration in humans and animals, however the healing potential of ligament is poor and current treatment options ineffective. Stem cell-based therapies hold potential for treatment of ligament injuries. This study aimed to characterize a ligament progenitor cell (LPC) population and to identify specific niche components which could promote the survival and function of LPCs. LPCs were isolated from canine cranial cruciate ligament and characterized for clonogenicity, multipotency and marker expression. The extracellular matrix (ECM) composition was characterized by the novel application of a metabolic labeling and mass spectrometry technique. LPCs demonstrated clonogenicity, multipotency, and stem cell marker expression. A number of different collagens, glycoproteins, and proteoglycans were identified in the LPC niche using proteomics. Metabolic labeling of cells demonstrated unique turnover profiles for distinct ECM protein groups, indicating the importance of certain niche components for LPC survival and function. The newly synthesized niche components identified in this study could be exploited to aid identification of LPCs and to promote their survival and function for potential ligament repair strategies.
MeSH term(s)	Animals ; Anterior Cruciate Ligament/cytology ; Anterior Cruciate Ligament/transplantation ; Cell Lineage/genetics ; Collagen/genetics ; Collagen/metabolism ; Colony-Forming Units Assay ; Dogs ; Extracellular Matrix/genetics ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/isolation & purification ; Extracellular Matrix Proteins/metabolism ; Gene Expression Regulation, Developmental/genetics ; Humans ; Liver/metabolism ; Proteoglycans/genetics ; Stem Cell Niche/genetics ; Stem Cells/cytology ; Stem Cells/metabolism
Chemical Substances	Extracellular Matrix Proteins ; Proteoglycans ; Collagen (9007-34-5)
Language	English
Publishing date	2019-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.8b00933
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Article ; Online: Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice

Katie J. Lee / Lisa Rambault / George Bou-Gharios / Peter D. Clegg / Riaz Akhtar / Gabriela Czanner / Rob van ‘t Hof / Elizabeth G. Canty-Laird

Disease Models & Mechanisms, Vol 15, Iss

2022 Volume 9

Keywords	collagen ; homotrimer ; col1a2 ; α2(i) ; osteogenesis imperfecta ; cveds ; Medicine ; R ; Pathology ; RB1-214
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Variations in internal structure, composition and protein distribution between intra- and extra-articular knee ligaments and tendons.

Kharaz, Yalda A / Canty-Laird, Elizabeth G / Tew, Simon R / Comerford, Eithne J

Journal of anatomy

2018 Volume 232, Issue 6, Page(s) 943–955

Abstract: Tendons and ligaments play key roles in the musculoskeletal system in both man and animals. Both tissues can undergo traumatic injury, age-related degeneration and chronic disease, causing discomfort, pain and increased susceptibility to wider ... ...

Abstract	Tendons and ligaments play key roles in the musculoskeletal system in both man and animals. Both tissues can undergo traumatic injury, age-related degeneration and chronic disease, causing discomfort, pain and increased susceptibility to wider degenerative joint disease. To date, tendon and ligament ultrastructural biology is relatively under-studied in healthy, non-diseased tissues. This information is essential to understand the pathology of these tissues with regard to function-related injury and to assist with the future development of tissue-engineered tendon and ligament structures. This study investigated the morphological, compositional and extracellular matrix protein distribution differences between tendons and ligaments around the non-diseased canine stifle joint. The morphological, structural characteristics of different regions of the periarticular tendons and ligaments (the intra-articular anterior cruciate ligament, the extra-articular medial collateral ligament, the positional long digital extensor tendon and energy-storing superficial digital flexor tendons) were identified using a novel semi-objective histological scoring analysis and by determining their biochemical composition. Protein distribution of extracellular matrix collagens, proteoglycans and elastic fibre proteins in anterior cruciate ligament and long digital extensor tendon were also determined using immunostaining techniques. The anterior cruciate ligament was found to have significant morphological differences in comparison with the other three tissues, including less compact collagen architecture, differences in cell nuclei phenotype and increased glycosaminoglycan and elastin content. Intra- and interobserver differences of histology scoring resulted in an average score 0.7, indicative of good agreement between observers. Statistically significant differences were also found in the extracellular matrix composition in terms of glycosaminoglycan and elastin content, being more prominent in the anterior cruciate ligament than in the other three tissues. A different distribution of several extracellular matrix proteins was also found between long digital extensor tendon and anterior cruciate ligament, with a significantly increased immunostaining of aggrecan and versican in the anterior cruciate ligament. These findings directly relate to the different functions of tendon and ligament and indicate that the intra-articular anterior cruciate ligament is subjected to more compressive forces, reflecting an adaptive response to normal or increased loads and resulting in different extracellular matrix composition and arrangement to protect the tissue from damage.
MeSH term(s)	Animals ; Dogs ; Knee Joint/anatomy & histology ; Knee Joint/chemistry ; Knee Joint/metabolism ; Ligaments/anatomy & histology ; Ligaments/chemistry ; Ligaments/metabolism ; Tendons/anatomy & histology ; Tendons/chemistry ; Tendons/metabolism
Language	English
Publishing date	2018-03-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2955-5
ISSN	1469-7580 ; 0021-8782
ISSN (online)	1469-7580
ISSN	0021-8782
DOI	10.1111/joa.12802
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Article: Cross-species gene modules emerge from a systems biology approach to osteoarthritis.

Mueller, Alan James / Canty-Laird, Elizabeth G / Clegg, Peter D / Tew, Simon R

NPJ systems biology and applications

2017 Volume 3, Page(s) 13

Abstract: Complexities in degenerative disorders, such as osteoarthritis, arise from multiscale biological, environmental, and temporal perturbations. Animal models serve to provide controlled representations of the natural history of degenerative disorders, but ... ...

Abstract	Complexities in degenerative disorders, such as osteoarthritis, arise from multiscale biological, environmental, and temporal perturbations. Animal models serve to provide controlled representations of the natural history of degenerative disorders, but in themselves represent an additional layer of complexity. Comparing transcriptomic networks arising from gene co-expression data across species can facilitate an understanding of the preservation of functional gene modules and establish associations with disease phenotypes. This study demonstrates the preservation of osteoarthritis-associated gene modules, described by immune system and system development processes, across human and rat studies. Class prediction analysis establishes a minimal gene signature, including the expression of the Rho GDP dissociation inhibitor
Language	English
Publishing date	2017-05-17
Publishing country	England
Document type	Journal Article
ISSN	2056-7189
ISSN	2056-7189
DOI	10.1038/s41540-017-0014-3
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Article ; Online: Proteomic differences between native and tissue-engineered tendon and ligament.

Kharaz, Yalda A / Tew, Simon R / Peffers, Mandy / Canty-Laird, Elizabeth G / Comerford, Eithne

Proteomics

2016 Volume 16, Issue 10, Page(s) 1547–1556

Abstract: Tendons and ligaments (T/Ls) play key roles in the musculoskeletal system, but they are susceptible to traumatic or age-related rupture, leading to severe morbidity as well as increased susceptibility to degenerative joint diseases such as osteoarthritis. ...

Abstract	Tendons and ligaments (T/Ls) play key roles in the musculoskeletal system, but they are susceptible to traumatic or age-related rupture, leading to severe morbidity as well as increased susceptibility to degenerative joint diseases such as osteoarthritis. Tissue engineering represents an attractive therapeutic approach to treating T/L injury but it is hampered by our poor understanding of the defining characteristics of the two tissues. The present study aimed to determine differences in the proteomic profile between native T/Ls and tissue engineered (TE) T/L constructs. The canine long digital extensor tendon and anterior cruciate ligament were analyzed along with 3D TE fibrin-based constructs created from their cells. Native tendon and ligament differed in their content of key structural proteins, with the ligament being more abundant in fibrocartilaginous proteins. 3D T/L TE constructs contained less extracellular matrix (ECM) proteins and had a greater proportion of cellular-associated proteins than native tissue, corresponding to their low collagen and high DNA content. Constructs were able to recapitulate native T/L tissue characteristics particularly with regard to ECM proteins. However, 3D T/L TE constructs had similar ECM and cellular protein compositions indicating that cell source may not be an important factor for T/L tissue engineering.
MeSH term(s)	Animals ; Anterior Cruciate Ligament/cytology ; Anterior Cruciate Ligament/metabolism ; Cells, Cultured ; Dogs ; Extracellular Matrix/metabolism ; Patellar Ligament/cytology ; Patellar Ligament/metabolism ; Proteome/metabolism ; Proteomics ; Tissue Culture Techniques ; Tissue Engineering
Chemical Substances	Proteome
Language	English
Publishing date	2016-04-15
Publishing country	Germany
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2032093-0
ISSN	1615-9861 ; 1615-9853
ISSN (online)	1615-9861
ISSN	1615-9853
DOI	10.1002/pmic.201500459
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Zs.A 5386: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 1868: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Cross-species gene modules emerge from a systems biology approach to osteoarthritis

Alan James Mueller / Elizabeth G. Canty-Laird / Peter D. Clegg / Simon R. Tew

npj Systems Biology and Applications, Vol 3, Iss 1, Pp 1-

2017 Volume 15

Abstract: Joint degeneration: linking animal and human disease Cartilage, and other tissues in our joints, begins to degenerate with age resulting in pain and reduced mobility; this is termed osteoarthritis (OA). To understand OA better researchers have often used ...

Abstract	Joint degeneration: linking animal and human disease Cartilage, and other tissues in our joints, begins to degenerate with age resulting in pain and reduced mobility; this is termed osteoarthritis (OA). To understand OA better researchers have often used animal models to represent this disease; however, these models have never been fully-evaluated against human cartilage. This study considered the messages produced by cartilage cells in both humans and rats. Using a method that creates a network of messages the study was able to define “blocks” of cell messages that were associated with diseased cartilage in both the rat and human. As part of this study the authors also defined a set of messages that could be used to distinguish healthy and disease cartilage. In this way it may be possible to define patients with early OA that may benefit from therapeutic interventions. (135)
Keywords	Biology (General) ; QH301-705.5
Subject code	616 ; 006
Language	English
Publishing date	2017-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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