Ageing does not result in a decline in cell synthetic activity in an injury prone tendon.
Abstract: Advancing age is a well-known risk factor for tendon disease. Energy-storing tendons [e.g., human Achilles, equine superficial digital flexor tendon (SDFT)] are particularly vulnerable and it is thought that injury occurs following an accumulation of micro-damage in the extracellular matrix (ECM). Several authors suggest that age-related micro-damage accumulates due to a failure of the aging cell population to maintain the ECM or an imbalance between anabolic and catabolic pathways. We hypothesized that ageing results in a decreased ability of tendon cells to synthesize matrix components and matrix-degrading enzymes, resulting in a reduced turnover of the ECM and a decreased ability to repair micro-damage. The SDFT was collected from horses aged 3-30 years with no signs of tendon injury. Cell synthetic and degradative ability was assessed at the mRNA and protein levels. Telomere length was measured as an additional marker of cell ageing. There was no decrease in cellularity or relative telomere length with increasing age, and no decline in mRNA or protein levels for matrix proteins or degradative enzymes. The results suggest that the mechanism for age-related tendon deterioration is not due to reduced cellularity or a loss of synthetic functionality and that alternative mechanisms should be considered.
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Publication Date: 2015-06-09 PubMed ID: 26058332DOI: 10.1111/sms.12500Google Scholar: Lookup
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- Journal Article
Summary
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The research investigates whether advancing age results in lower rates of cell synthesis and repair in tendons, namely the equine superficial digital flexor tendon (SDFT). It concludes that ageing does not appear to decrease the capability of tendon cells to produce matrix components and matrix-degrading enzymes significant for tendon repair.
Objective and Hypothesis
- The objective of the research was to determine if advancing age impacts the cell synthetic functionality in injury prone tendons, using the equine superficial digital flexor tendon (SDFT) as the subject of the study.
- The researchers hypothesized that advancing age decreases the tendon cells’ ability to synthesize matrix components and degrade enzymes, which would result in reduced turnover of the extracellular matrix (ECM) and a diminished capacity to repair micro-damage.
Methodology and Analysis
- The SDFT was collected from horses aged 3 to 30 years having no signs of tendon injury to ensure that the samples were not compromised.
- The researchers assessed the cell synthetic and degradative abilities at both the mRNA and protein levels. This was meant to determine whether there was a decline in the production of matrix proteins or degradative enzymes that are key in maintaining the extracellular matrix (ECM).
- The team also measured the telomere length, a known marker of cell ageing, to see if there was a decrease in this aspect with increasing age.
Findings
- Contrary to their hypothesis, the researchers found that there was no decline in the cellularity, relative telomere length, mRNA or protein levels for matrix proteins or degrading enzymes as the age increased.
- This suggests that the age-related tendon deterioration is not a result of reduced cellularity or a loss in the generation of important ECM components and enzymes.
- It suggests that alternative mechanisms might be behind the age-related tendon degeneration rather than a decrease in cell synthetic activity.
Cite This Article
APA
Thorpe CT, McDermott BT, Goodship AE, Clegg PD, Birch HL.
(2015).
Ageing does not result in a decline in cell synthetic activity in an injury prone tendon.
Scand J Med Sci Sports, 26(6), 684-693.
https://doi.org/10.1111/sms.12500 Publication
Researcher Affiliations
- Institute of Orthopaedics and Musculoskeletal Science, Royal National Orthopaedic Hospital, University College London, Stanmore, UK.
- Department of Musculoskeletal Biology, University of Liverpool, Cheshire, UK.
- Institute of Orthopaedics and Musculoskeletal Science, Royal National Orthopaedic Hospital, University College London, Stanmore, UK.
- Department of Musculoskeletal Biology, University of Liverpool, Cheshire, UK.
- Institute of Orthopaedics and Musculoskeletal Science, Royal National Orthopaedic Hospital, University College London, Stanmore, UK.
MeSH Terms
- ADAM12 Protein / genetics
- ADAM17 Protein / genetics
- ADAMTS Proteins / genetics
- Aging / metabolism
- Aging / pathology
- Animals
- DNA / metabolism
- Extracellular Matrix / physiology
- Horses
- Matrix Metalloproteinases / genetics
- Matrix Metalloproteinases / metabolism
- Peptide Fragments / biosynthesis
- Procollagen / biosynthesis
- RNA, Messenger / metabolism
- Telomere Shortening
- Tendons / cytology
- Tendons / enzymology
- Tendons / metabolism
- Tissue Inhibitor of Metalloproteinase-3 / genetics
- Tissue Inhibitor of Metalloproteinases / genetics
Grant Funding
- MR/K006312/1 / Medical Research Council
Citations
This article has been cited 9 times.- Siadat SM, Zamboulis DE, Thorpe CT, Ruberti JW, Connizzo BK. Tendon Extracellular Matrix Assembly, Maintenance and Dysregulation Throughout Life.. Adv Exp Med Biol 2021;1348:45-103.
- Yin NH, Parker AW, Matousek P, Birch HL. Detection of Age-Related Changes in Tendon Molecular Composition by Raman Spectroscopy-Potential for Rapid, Non-Invasive Assessment of Susceptibility to Injury.. Int J Mol Sci 2020 Mar 20;21(6).
- Lui PPY, Wong CM. Biology of Tendon Stem Cells and Tendon in Aging.. Front Genet 2019;10:1338.
- Ribitsch I, Gueltekin S, Keith MF, Minichmair K, Peham C, Jenner F, Egerbacher M. Age-related changes of tendon fibril micro-morphology and gene expression.. J Anat 2020 Apr;236(4):688-700.
- Connizzo BK, Piet JM, Shefelbine SJ, Grodzinsky AJ. Age-associated changes in the response of tendon explants to stress deprivation is sex-dependent.. Connect Tissue Res 2020 Jan;61(1):48-62.
- Turlo AJ, Ashraf Kharaz Y, Clegg PD, Anderson J, Peffers MJ. Donor age affects proteome composition of tenocyte-derived engineered tendon.. BMC Biotechnol 2018 Jan 16;18(1):2.
- Gagliano N, Menon A, Cabitza F, Compagnoni R, Randelli P. Morphological and molecular characterization of human hamstrings shows that tendon features are not influenced by donor age.. Knee Surg Sports Traumatol Arthrosc 2018 Jan;26(1):343-352.
- Ackerman JE, Bah I, Jonason JH, Buckley MR, Loiselle AE. Aging does not alter tendon mechanical properties during homeostasis, but does impair flexor tendon healing.. J Orthop Res 2017 Dec;35(12):2716-2724.
- Johnston JM, Connizzo BK, Shetye SS, Robinson KA, Huegel J, Rodriguez AB, Sun M, Adams SM, Birk DE, Soslowsky LJ. Collagen V haploinsufficiency in a murine model of classic Ehlers-Danlos syndrome is associated with deficient structural and mechanical healing in tendons.. J Orthop Res 2017 Dec;35(12):2707-2715.
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