Dramatic regulation of heparanase activity and angiogenesis gene expression in synovium from patients with rheumatoid arthritis.
OBJECTIVE
Although heparanase is recognized as a proangiogenic factor, the involvement of heparanase in rheumatoid arthritis (RA) is unclear. In this study, we assessed heparanase activity in synovial fluid (SF) and synovial tissue (ST) from patients with RA or osteoarthritis (OA), and analyzed the expression of angiogenic pathway-focused genes in ST from RA and OA patients.


METHODS
SF and ST were obtained from the knees of patients with either RA or OA and from asymptomatic donors with no documented history of degenerative or inflammatory joint diseases. Heparanase activity was determined by an enzymatic assay using a radiolabeled substrate, and the presence of heparanase in ST was demonstrated by Western blotting. The expression of angiogenesis genes, including heparanase, in ST was analyzed by real-time quantitative polymerase chain reaction.


RESULTS
Heparanase activity was dramatically higher (>100-fold) in SF and ST from RA patients than in SF and ST from OA patients and asymptomatic donors. Active heparanase enzyme was detected and heparanase messenger RNA was up-regulated in ST from RA patients. We also found that angiogenesis gene expression was significantly regulated in RA synovium, and was correlated with heparanase activity.


CONCLUSIONS
These findings are novel and contribute to our understanding of joint destruction in RA, suggesting that heparanase may be a reliable prognostic factor for RA progression and an attractive target for the treatment of RA.
Li
Rachel W
RW
Australian National University, and Canberra Hospital, Canberra, ACT, Australia. rachel.li@anu.edu.au
Freeman
Craig
C
Yu
Di
D
Hindmarsh
Elizabeth J
EJ
Tymms
Kathleen E
KE
Parish
Christopher R
CR
Smith
Paul N
PN
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D013582:Synovial Fluid / Q000201:enzymology*; D013583:Synovial Membrane / Q000201:enzymology*; D000099175:Heparanase
D005966:Glucuronidase; D012333:RNA, Messenger; D000099175:Heparanase