R. Vallon et al., Serum amyloid A (apoSAA) expression is up-regulated in rheumatoid arthritis and induces transcription of matrix metalloproteinases, J IMMUNOL, 166(4), 2001, pp. 2801-2807
The acute-phase reactant rabbit serum amyloid A 3 (SAA3) was identified as
the major difference product in Ag-induced arthritis in the rabbit, a model
resembling in many aspects the clinical characteristics of rheumatoid arth
ritis (RA) in humans. In Ag-induced arthritis, up-regulated SAA3 transcript
ion in vivo was detected in cells infiltrating into the inflamed joint, in
the area where pannus formation starts and, most notably, also in chondrocy
tes. The proinflammatory cytokine IL-1 beta induced SAA3 transcription in p
rimary rabbit chondrocytes in vitro. Furthermore, rSAA3 protein induced tra
nscription of matrix metalloproteinases in rabbit chondrocytes in vitro. In
the human experimental system, IL-1 beta induced transcription of acute-ph
ase SAA (A-SSA; encoded by SAA1/SAA2) in primary chondrocytes. Similar to t
he rabbit system, recombinant human A-SAA protein was able to induce matrix
metalloproteinases' transcription in chondrocytes. Further, immunohistoche
mistry demonstrated that A-SAA was highly expressed in human RA synovium, A
new finding of our study is that A-SSA expression was also detected in car
tilage in osteoarthritis. Our data, together with previous findings of SAA
expression in RA synovium, suggest that A-SAA may play a role in cartilage
destruction in arthritis.