Induction of fibroblast-like cells from CD34(+) progenitor cells of the bone marrow in rheumatoid arthritis.
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 alpha (TNF-alpha), 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-alpha. 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-alpha-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-alpha 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.
Hirohata
S
S
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan. shunsei@med.teikyo-u.ac.jp
Yanagida
T
T
Nagai
T
T
Sawada
T
T
Nakamura
H
H
Yoshino
S
S
Tomita
T
T
Ochi
T
T
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis*; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D008875:Middle Aged; D011393:Procollagen-Proline Dioxygenase / Q000096:biosynthesis; D019089:Stem Cell Factor / Q000494:pharmacology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D013583:Synovial Membrane / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018952:Antigens, CD34; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011393:Procollagen-Proline Dioxygenase; D020781:Matrix Metalloproteinase 1