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

  • Original Article
  • Published:
Journal of Orthopaedic Science

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.

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Acknowledgments

We gratefully acknowledge the technical assistance of Miyuki Murayama and Mizuho Kosuge. Financial support for this study was provided by a Grant-in-Aid for Scientific Research (C).

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan

    Koichiro Tanaka, Keisuke Horiuchi, Katsuhito Takeuchi, Yoshiaki Toyama & Hideo Morioka

  2. Department of Orthopaedic Surgery, Kyorin University, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

    Takeshi Morii

  3. Sarcoma Molecular Biology Laboratory, Massachusetts General Hospital, 70 Blossom Street, MGR J 1115, Boston, MA, 02114, USA

    Lawrence Weissbach

Authors
  1. Koichiro Tanaka
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  2. Takeshi Morii
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  3. Lawrence Weissbach
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  4. Keisuke Horiuchi
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  5. Katsuhito Takeuchi
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  6. Yoshiaki Toyama
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  7. Hideo Morioka
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Corresponding author

Correspondence to Koichiro Tanaka.

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Tanaka, K., Morii, T., Weissbach, L. et al. Treatment of collagen-induced arthritis with recombinant plasminogen-related protein B: a novel inhibitor of angiogenesis. J Orthop Sci 16, 443–450 (2011). https://doi.org/10.1007/s00776-011-0091-x

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  • DOI: https://doi.org/10.1007/s00776-011-0091-x

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