G. Cunnane et al., Collagenase, cathepsin B and cathepsin L gene expression in the synovial membrane of patients with early inflammatory arthritis, RHEUMATOLOG, 38(1), 1999, pp. 34-42
Objective. To examine the expression of the matrix metalloproteinase, MMP-1
, and the cysteine proteases, cathepsin B (CB) and cathepsin L (CL), in the
synovial membrane (SM) of patients with early inflammatory arthritis.
Methods. Samples of SM were obtained by blind needle biopsy or needle arthr
oscopy from inflamed knees of 28 patients with early inflammatory arthritis
(mean disease duration 10.2 months, range 2 weeks-18 months). Sixteen pati
ents had rheumatoid arthritis (RA), nine psoriatic arthritis and there was
one each with ankylosing spondylitis, gout and an undifferentiated arthriti
s. Comparison was made with tissue from two patients with established erosi
ve RA and three normal synovial tissue samples. In situ hybridization was p
erformed using digoxigenin-labelled RNA probes.
Results. MMP-1, CB and CL were expressed in all patients with early arthrit
is and in established erosive RA, whereas normal synovium showed only scant
y expression. The three proteases were prominent in perivascular infiltrate
s and endothelial cells of early arthritis tissue. MMP-1 was observed prima
rily in the lining layer, but was also evident in the sublining area. CB an
d CL were expressed to a lesser extent in the lining layer, and were presen
t mainly in the subintima. The three proteases were not found in lymphoid a
ggregrates. No differences were observed between the disease categories.
Conclusions. The detection of MMP-1, CB and CL in the synovium shortly afte
r symptom onset implies that the potential for joint destruction exists at
a very early stage in the disease. In addition. the perivascular and endoth
elial cell expression suggests a role for these proteases in mononuclear ce
ll influx to the inflamed synovium and in angiogenesis.