Inhibition of arthritis by systemic administration of endostatin in passive murine collagen induced arthritis

Abstract

Objective: To investigate the arthritis inhibiting effect of endostatin, known to have potent antiangiogenic activity, systemically given to animal models of rheumatoid arthritis (RA). Methods: Four kinds of monoclonal anti-type II collagen antibody followed by lipopolysaccharide (LPS) three days later were given to 6 week old, female Balb/c mice to induce arthritis. Three groups of mice received 0.2 mg/kg/day, 2 mg/kg/day, and 10 mg/kg/day of endostatin, respectively, whereas a control group received phosphate buffered saline (PBS). Endostatin or PBS was given for 13 days, starting before the development of arthritis. Arthritis was evaluated by arthritis scores and hind paw thicknesses. Mice were killed for histological examination on the 22nd day after the administration of monoclonal anti-type II collagen antibody. Results: Arthritis developed within three days after LPS administration in both the control and endostatin treatment groups. No difference in the development rate of arthritis was noted between the control and endostatin treatment groups. Arthritis scores remained significantly lower in the endostatin 10 mg/kg/day group than in the control group. Hind paw thicknesses also remained significantly smaller in the endostatin 10 mg/kg/day group than in the control group. Histopathological examination showed that synovial thickening and subchondral bone erosion improved more in the endostatin treatment groups than in the control group. Conclusion: The systemic administration of endostatin had an arthritis inhibiting effect in RA animal models. Endostatin inhibited, in particular, pannus formation and bone destruction.

Inhibition of corneal neovascularization with endostatin delivered by adeno-associated viral (AAV) vector in a mouse corneal injury model

“…The endostatin gene was even retrovirally transduced to tumor cells and the transduced cells were subsequently xenotransplanted in a murine tumor model [27]. Kurosaka et al [28] reported that systemic administration of endostatin can inhibit pannus formation and bone destruction in arthritis. Jung et al [29] showed that recombinant endostatin protein inhibits the proliferation of neovascularization in a human placental vessel vein disk model.…”

The effect of endostatin evaluated in an experimental animal model of collagen‐induced arthritis

“…Yin et al reported that the injection of lentiviral vectors, which had been engineered to express the endostatin gene, directly into the joints of arthritis mice improved the arthritis (8). Both our group (9) and Yue et al (10) reported anti-arthritic effects of systemically administered endostatin. We administered recombinant endostatin to mice with antibody-induced arthritis before the development of arthritis, and observed them for arthritis-inhibiting effects.…”

Recombinant human endostatin inhibits adjuvant arthritis by down-regulating VEGF expression and suppression of TNF-α, IL-1β production

“…Endostatin has been found to stop the growth of Lewis lung carcinoma experimental metastases in mice without signs of toxicity and to specifically inhibit the growth of several primary tumors [13,14]. It has also been shown to have potent therapeutic effect on arthritis [6,15,16]. In the current study, we investigated the effects of rhEndostatin on the AA rat, which might improve symptoms of the disease through inhibition of proangiogenic and proinflammatory cytokines.…”