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(Journal of Leukocyte Biology. 2001;70:413-421.)
© 2001 by Society for Leukocyte Biology

Induction of fibroblast-like cells from CD34⁺ progenitor cells of the bone marrow in rheumatoid arthritis

Shunsei Hirohata^*, Tamiko Yanagida^*, Tatsuo Nagai, Tetsuji Sawada, Hiroshi Nakamura, Shin’ichi Yoshino, Tetsuya Tomita^|| and Takahiro Ochi^||

^* Department of Internal Medicine, Teikyo University School of Medicine,
Department of Allergy and Rheumatology, University of Tokyo School of Medicine, and
Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo;
Rheumatology and Immunology, Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa; and
^|| Department of Orthopedic Surgery, Osaka University Medical School, Japan

Correspondence: Shunsei Hirohata, MD, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan. E-mail: shunsei{at}med.teikyo-u.ac.jp

To assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA), we examined the capacity of CD34⁺ cells from bone marrow to generate fibroblast-like type B synoviocytes. CD34⁺ cells from the bone marrow of 22 RA patients differentiated into cells with fibroblast-like morphology, which expressed prolyl 4-hydroxylase, in the presence of stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF-), much more effectively than CD34⁺ cells from bone marrow of 15 control subjects (10 patients with osteoarthritis and 5 healthy individuals). The generation of fibroblast-like cells was not at all observed in cultures with SCF, GM-CSF, and interleukin 4 (IL-4) with or without TNF-. Generation of fibroblast-like cells was correlated with matrix metalloproteinase (MMP)-1 levels in culture supernatants. Thus, MMP-1 levels were significantly higher in TNF--stimulated cultures of bone marrow CD34⁺ cells from patients with RA than in those from the control group. These results indicate that bone marrow CD34⁺ cells from patients with RA have abnormal capacities to respond to TNF- and to differentiate into fibroblast-like cells producing MMP-1, suggesting that bone marrow CD34⁺ progenitor cells might generate type B synoviocytes and thus could play an important role in the pathogenesis of RA.

Key Words: cytokines • matrix metalloproteinase 1 • prolyl 4-hydroxylase

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