Our aim was to correlate the activity of matrix metalloproteinases (MMPs) with denaturation
and the turnover of collagen in normal and pathological human tendons. MMPs were extracted
from ruptured supraspinatus tendons (n=10), macroscopically normal ("control") supraspinatus
tendons (n=29) and normal short head of biceps brachii tendons (n=24). Enzyme activity
was measured using fluorogenic substrates selective for MMP-1, MMP-3 and enzymes with
gelatinolytic activity (MMP-2, MMP-9 and MMP-13). Collagen denaturation was determined
by alpha-chymotrypsin digestion. Protein turnover was determined by measuring the
percentage of D-aspartic acid (% D-Asp). Zymography was conducted to identity specific
gelatinases. MMP-1 activity was higher in ruptured supraspinatus compared to control
supraspinatus and normal biceps brachii tendons (70.9, 26.4 and 11.5 fmol/mg tendon,
respectively; P<0.001). Gelatinolytic and MMP-3 activities were lower in normal biceps
brachii and ruptured supraspinatus compared to control supraspinatus (gelatinase:
0.18, 0.23 and 0.82 RFU/s/mg tendon respectively; P<0.001; MMP-3: 9.0, 8.6 and 55
fmol/mg tendon, respectively; P<0.001). Most gelatinase activity was shown to be MMP-2
by zymography. Denatured collagen was increased in ruptured supraspinatus compared
to control supraspinatus (20.4% and 9.9%, respectively; P<0.001). The % D-Asp content
increased linearly with age in normal biceps brachii but not in control supraspinatus
and was significantly lower in ruptured supraspinatus compared to age-matched control
tendons (0.33 and 1.09% D-Asp, respectively; P<0.01). We conclude that the short head
of biceps brachii tendons show little protein turnover, whereas control supraspinatus
tendons show relatively high turnover mediated by the activity of MMP-2, MMP-3 and
MMP-1. This activity is thought to represent a repair or maintenance function that
may be associated with an underlying degenerative process caused by a history of repeated
injury and/or mechanical strain. After tendon rupture, there was increased activity
of MMP-1, reduced activity of MMP-2 and MMP-3, increased turnover and further deterioration
in the quality of the collagen network. Tendon degeneration is shown to be an active,
cell-mediated process that may result from a failure to regulate specific MMP activities
in response to repeated injury or mechanical strain.