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Induction of vascular endothelial growth factor and matrix metalloproteinase-3 (stromelysin) by interleukin-1 in human articular chondrocytes and synoviocytes

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Abstract

We investigated the effects of interleukin (IL)-1 on vascular endothelial growth factor (VEGF) and matrix metalloproteinase-3 (MMP-3) (stromelysin) secretion from chondrocytes and synoviocytes in different clinical conditions. Specifically, cells obtained from osteoarthritic (OA) (n=7), rheumatoid arthritic (RA) (n=5), and post-traumatic (PT) (n=5) patients were stimulated in vitro with IL-1β in the presence or absence of an IL-1 receptor antagonist (IL-1ra) (anakinra). Levels of secreted MMP-3 and VEGF were measured by enzyme-linked immunosorbent assay. The VEGF mRNA expression was analyzed quantitatively. Interleukin-1 induced both VEGF and MMP-3 secretion from all of the samples tested, and VEGF mRNA expression was also upregulated. Interleukin-1ra significantly suppressed the enhancing effect of IL-1 on MMP-3 and VEGF in both cell types. In conclusion, IL-1 simultaneously induces MMP-3 and VEGF production from chondrocytes and synoviocytes in inflammatory, degenerative, and post-traumatic joints. Therefore, IL-1ra might be beneficial for protection from VEGF-mediated alterations of cartilage metabolism in pathologic and physiologic conditions.

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Acknowledgements

The authors thank Dr. Atsuyuki Shibakawa and Prof. Haruhito Aoki of the Department of Orthopedic Surgery, St. Marianna University School of Medicine, for clinical samples and important advice. We also appreciate Ms. Toshiko Mogi and Ms. Hiroe Ogasawara for their excellent technical assistance and Ms. Maki Kitagaki for secretarial assistance. This study was supported by a grant from Amgen.

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  1. Division of Molecular Regulation, Department of Bioregulation, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216-8512, Japan

    Kenji Inoue, Kayo Masuko-Hongo, Masahiro Okamoto & Kusuki Nishioka

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  1. Kenji Inoue
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  2. Kayo Masuko-Hongo
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  3. Masahiro Okamoto
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  4. Kusuki Nishioka
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Correspondence to Kayo Masuko-Hongo.

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Inoue, K., Masuko-Hongo, K., Okamoto, M. et al. Induction of vascular endothelial growth factor and matrix metalloproteinase-3 (stromelysin) by interleukin-1 in human articular chondrocytes and synoviocytes. Rheumatol Int 26, 93–98 (2005). https://doi.org/10.1007/s00296-004-0513-6

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  • DOI: https://doi.org/10.1007/s00296-004-0513-6

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