Y. Waguri-nagaya et al., Synovial inflammation and hyperplasia induced by gliostatin/platelet-derived endothelial cell growth factor in rabbit knees, RHEUM INTL, 20(1), 2000, pp. 13-19
Neovascularization, proliferation of synovial cells, and mononuclear cell i
nflux and activation are characteristic events observed in synovial joints
in the pathohistology of rheumatoid arthritis (RA). The objective of this s
tudy was to examine synovial inflammation in rabbit knees induced by intra-
articular administration of human gliostatin/platelet-derived endothelial c
ell growth factor (GLS/PD-ECGF), which shares a high degree of chemical hom
ology with thymidine phosphorylase (dThdPase) and is known to have angiogen
ic activity. Purified recombinant human gliostatin (rHuGLS) and its mutant
protein, which was prepared by site-directed mutagenesis and which lacks dT
hdPase activity, were administered at various doses to rabbit knee joints.
The effects of rHuGLS and the mutant were examined histologically. Intra-ar
ticular injection of rHuGLS resulted in the development of diffuse synoviti
s resembling RA. The mutant protein also brought about the same effect. The
se findings suggest that human GLS carl cause RA-like synovitis in rabbit k
nee joints via a mechanism other than its dThdPase activity.