Open AccessAging enhances a mechanically‐induced reduction in tendon strength by an active process involving matrix metalloproteinase activity
Author(s) -
Dudhia Jayesh,
Scott Charlotte M.,
Draper Edward R. C.,
Heinegård Dick,
Pitsillides Andrew A.,
Smith Roger K.
Publication year - 2007
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2007.00307.x
Subject(s) - tendon , matrix metalloproteinase , extracellular matrix , ultimate tensile strength , fibronectin , cartilage oligomeric matrix protein , biology , microbiology and biotechnology , materials science , anatomy , pathology , medicine , biochemistry , osteoarthritis , composite material , alternative medicine
Summary 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.