Treatment with the angiogenesis inhibitor endostatin: a novel therapy in rheumatoid arthritis.
OBJECTIVE
An endostatin that inhibits angiogenesis dependent tumor growth is being tested as an antitumor agent. The neoangiogenesis condition of cancer is essentially identical to that of rheumatoid arthritis (RA). Thus antiangiogenic treatment has potential for treatment of RA. We investigated the effects of human recombinant endostatin on human RA synovial tissue by use of a novel model of RA, in which human RA tissue is grafted into SCID mice (SCID-HuRAg).


METHODS
Ten or 50 mg/kg of human recombinant endostatin was administered by percutaneous direct intrasynovial injection in each of 7 SCID-HuRAg mice. We examined the volume of the grafted tissue mass and the histological changes 7 days after endostatin administration. Six control mice received phosphate buffered saline in the same manner.


RESULTS
The grafted synovial volume of SCID-HuRAg mice was significantly decreased by endostatin administration. The number of inflammatory cells (macrophages and lymphocytes) was also significantly reduced in a dose dependent manner. The number of vessels that were counted by von Willebrand factor VIII and type IV collagen positive cells was decreased, although apoptotic cells were increased in RA synovia.


CONCLUSIONS
The results suggest that antiangiogenesis treatment using endostatin represents a potential new therapeutic strategy for RA.
Matsuno
Hiroaki
H
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan. matsuno@ms.toyama-mpu.ac.jp
Yudoh
Kazuo
K
Uzuki
Miwa
M
Nakazawa
Fujio
F
Sawai
Takashi
T
Yamaguchi
Noriko
N
Olsen
Bjorn R
BR
Kimura
Tomoatsu
T
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003094:Collagen / Q000494:pharmacology*; D043170:Collagen Type XVIII; D004195:Disease Models, Animal; D043169:Endostatins; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008833:Microcirculation; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D013583:Synovial Membrane / Q000098:blood supply / Q000276:immunology / Q000637:transplantation
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D003094:Collagen