Treatment of collagen-induced arthritis with recombinant plasminogen-related protein B: a novel inhibitor of angiogenesis.

Abstract

BACKGROUND:

We have previously reported that recombinant human plasminogen-related protein B (rPRP-B), a putative 9-kDa protein that closely resembles the activation peptide of plasminogen, has shown significant inhibition of tumor growth through inhibition of angiogenesis. Based on recent reports suggesting a close relationship between rheumatoid arthritis (RA) and angiogenesis, we hypothesized that this compound would regulate inflammatory conditions in RA. The present study therefore tested the effects of rPRP-B in the treatment of collagen-induced arthritis (CIA) to elucidate the mechanisms underlying these effects.

METHODS:

DBA/1J mice immunized with type II collagen to induce CIA were monitored to assess the effects of rPRP-B on clinical severity of the disease. Pathological changes in joints, including vessel formation and vascular endothelial growth factor (VEGF) production, were examined histologically. Bone destruction was radiologically evaluated. In vitro studies on the effects of rPRP-B on cell proliferation and production of VEGF in interleukin (IL)-1β or basic fibroblast growth factor (bFGF)-stimulated human synoviocytes were also performed.

RESULTS:

Development of CIA was effectively inhibited by rPRP-B. Radiological examinations revealed that the protein reduced bone destruction in CIA. CIA-induced vessel formation and VEGF expression in vivo were also reduced. In vitro mechanistic studies demonstrated that rPRP-B affected human synoviocyte proliferation and VEGF production stimulated by IL-1β and bFGF.

CONCLUSIONS:

Given the ability to effectively promote multistep anti-angiogenic activities, including cell growth inhibition and cytokine regulation, rPRP-B represents a promising candidate for a novel therapeutic agent against RA.

• Authors: Koichiro Tanaka, Takeshi Morii, Lawrence Weissbach, Keisuke Horiuchi, Katsuhito Takeuchi, Yoshiaki Toyama, Hideo Morioka
• Journal: Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association (J Orthop Sci) Vol. 16 Issue 4 Pg. 443-50 (Jul 2011) ISSN: 1436-2023 [Electronic] Japan
• PMID: 21584744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• PLGLB1 protein, human
• Recombinant Proteins
• Plasminogen

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Arthritis, Experimental (drug therapy)
• Male
• Mice
• Mice, Inbred DBA
• Plasminogen (therapeutic use)
• Recombinant Proteins (therapeutic use)