Serum amyloid A (apoSAA) expression is up-regulated in rheumatoid arthritis and induces transcription of matrix metalloproteinases.
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 arthritis (RA) in humans. In Ag-induced arthritis, up-regulated SAA3 transcription in vivo was detected in cells infiltrating into the inflamed joint, in the area where pannus formation starts and, most notably, also in chondrocytes. The proinflammatory cytokine IL-1beta induced SAA3 transcription in primary rabbit chondrocytes in vitro. Furthermore, rSAA3 protein induced transcription of matrix metalloproteinases in rabbit chondrocytes in vitro. In the human experimental system, IL-1beta induced transcription of acute-phase SAA (A-SSA; encoded by SAA1/SAA2) in primary chondrocytes. Similar to the rabbit system, recombinant human A-SAA protein was able to induce matrix metalloproteinases' transcription in chondrocytes. Further, immunohistochemistry 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 cartilage 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.
Vallon
R
R
Arthritis Biology, Department of Arthritis and Bone Metabolism, Novartis Pharma AG, Basle, Switzerland. ruediger.vallon@pharma.novartis.com
Freuler
F
F
Desta-Tsedu
N
N
Robeva
A
A
Dawson
J
J
Wenner
P
P
Engelhardt
P
P
Boes
L
L
Schnyder
J
J
Tschopp
C
C
Urfer
R
R
Baumann
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D019902:Chondrocytes / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D013583:Synovial Membrane / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases