title: Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity.
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 collide 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 <or= 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 <or= 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.
authors.affiliation: Department of Veterinary Clinical Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK. jdudhia@rvc.ac.uk
authors.forename: Jayesh
authors.initials: J
authors.lastname: Dudhia
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Scott
authors.forename: Edward R C
authors.initials: ER
authors.lastname: Draper
authors.forename: Dick
authors.initials: D
authors.lastname: Heinegård
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Pitsillides
authors.forename: Roger K
authors.initials: RK
authors.lastname: Smith
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism; D006736:Horses; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009043:Motor Activity; D018482:Muscle, Skeletal; D013314:Stress, Mechanical; D052256:Tendinopathy; D013710:Tendons / Q000201:enzymology* / Q000502:physiology*; D013718:Tensile Strength
chemical_list: D020782:Matrix Metalloproteinases