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Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity

Dudhia, Jayesh; Scott, Charlotte M.; Draper, Edward R. C.; Heinegård, Dick LU ; Pitsillides, Andrew A. and Smith, Roger K. (2007) In Aging Cell 6(4). p.547-556
Abstract
Age-associated and degenerative loss of functional integrity in soft tissues develops from effects of cumulative and subtle changes in their extracellular matrix (ECM). The highly ordered tendon ECM provides the tissue with its tensile strength during loading. As age and exercise collude in the high incidence of tendinopathies, we hypothesized that aged tendons fail due to cumulative damage resulting from a combination of diminished matrix repair and fragmentation of ECM proteins induced by prolonged cyclical loading, and that this is an active cell-mediated process. We developed an equine tendon explant model to examine the effect of age on the influence of prolonged cyclical loading at physiologically relevant strain rates (5% strain, 1... (More)
Age-associated and degenerative loss of functional integrity in soft tissues develops from effects of cumulative and subtle changes in their extracellular matrix (ECM). The highly ordered tendon ECM provides the tissue with its tensile strength during loading. As age and exercise collude in the high incidence of tendinopathies, we hypothesized that aged tendons fail due to cumulative damage resulting from a combination of diminished matrix repair and fragmentation of ECM proteins induced by prolonged cyclical loading, and that this is an active cell-mediated process. We developed an equine tendon explant model to examine the effect of age on the influence of prolonged cyclical loading at physiologically relevant strain rates (5% strain, 1 Hz for 24 h) on tissue mechanical properties, loss of ECM protein and matrix metalloproteinase (MMP) expression. We show significantly diminished mechanical strength of cyclically loaded tissue compared to controls (39.7 +/- 12%, P <= 0.05) this reduction was dependent on the presence of both viable cells and metalloproteinase activity. Furthermore, tendon from older specimens was more susceptible to weakening (11-30 years, 50% P <= 0.05) compared to immature and young mature tissue (1-3 years, 34%; 4-10 years, 35%, respectively). Cyclical load also induced release of degraded cartilage oligomeric matrix protein, an integral ECM protein, an effect that could be mimicked by culture with fibronectin fragments. These findings indicate prolonged cyclical loading of physiological magnitude decreases tendon tensile strength by an active process, and that MMPs may contribute to loss of functional competence, exaggerated by age, via load-induced proteolytic disruption of the ECM. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
tensile strain, tendon, metalloproteinase, aging, extracellular matrix
in
Aging Cell
volume
6
issue
4
pages
547 - 556
publisher
Wiley-Blackwell
external identifiers
  • wos:000248088000015
  • scopus:34447626457
ISSN
1474-9726
DOI
10.1111/j.1474-9726.2007.00307.x
language
English
LU publication?
yes
id
090a4437-dc3b-4e2a-a2c2-534cee6006f6 (old id 646045)
date added to LUP
2007-12-11 19:43:44
date last changed
2017-11-05 03:44:45
@article{090a4437-dc3b-4e2a-a2c2-534cee6006f6,
  abstract     = {Age-associated and degenerative loss of functional integrity in soft tissues develops from effects of cumulative and subtle changes in their extracellular matrix (ECM). The highly ordered tendon ECM provides the tissue with its tensile strength during loading. As age and exercise collude in the high incidence of tendinopathies, we hypothesized that aged tendons fail due to cumulative damage resulting from a combination of diminished matrix repair and fragmentation of ECM proteins induced by prolonged cyclical loading, and that this is an active cell-mediated process. We developed an equine tendon explant model to examine the effect of age on the influence of prolonged cyclical loading at physiologically relevant strain rates (5% strain, 1 Hz for 24 h) on tissue mechanical properties, loss of ECM protein and matrix metalloproteinase (MMP) expression. We show significantly diminished mechanical strength of cyclically loaded tissue compared to controls (39.7 +/- 12%, P &lt;= 0.05) this reduction was dependent on the presence of both viable cells and metalloproteinase activity. Furthermore, tendon from older specimens was more susceptible to weakening (11-30 years, 50% P &lt;= 0.05) compared to immature and young mature tissue (1-3 years, 34%; 4-10 years, 35%, respectively). Cyclical load also induced release of degraded cartilage oligomeric matrix protein, an integral ECM protein, an effect that could be mimicked by culture with fibronectin fragments. These findings indicate prolonged cyclical loading of physiological magnitude decreases tendon tensile strength by an active process, and that MMPs may contribute to loss of functional competence, exaggerated by age, via load-induced proteolytic disruption of the ECM.},
  author       = {Dudhia, Jayesh and Scott, Charlotte M. and Draper, Edward R. C. and Heinegård, Dick and Pitsillides, Andrew A. and Smith, Roger K.},
  issn         = {1474-9726},
  keyword      = {tensile strain,tendon,metalloproteinase,aging,extracellular matrix},
  language     = {eng},
  number       = {4},
  pages        = {547--556},
  publisher    = {Wiley-Blackwell},
  series       = {Aging Cell},
  title        = {Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity},
  url          = {http://dx.doi.org/10.1111/j.1474-9726.2007.00307.x},
  volume       = {6},
  year         = {2007},
}