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 arthrit is (RA), we examined the capacity of CD34(+) cells from bone marrow to gene rate fibroblast-like type B synoviocytes. CD34(+) cells from the bone marro w of 22 RA patients differentiated into cells with fibroblastlike morpholog y, which expressed prolyl 4-hydroxylase, in the presence of stem cell facto r (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tum or necrosis factor alpha (TNF-alpha), much more effectively than CD34(+) ce lls from bone marrow of 15 control subjects (10 patients with osteoarthriti s and 5 healthy individuals). The generation of fibroblast-like cells was n ot at all observed in cultures with SCF, GM-CSF, and interleukin 4 (IL-4) w ith or without TNF-alpha. Generation of fibroblast-like cells was correlate d with matrix metalloproteinase (MMP)-1 levels in culture supernatants. Thu s, 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 p atients with RA have abnormal capacities to respond to TNF-alpha and to dif ferentiate into fibroblast-like cells producing MMP-1, suggesting that bone marrow CD34(+) progenitor cells might generate type B synoviocytes and thu s could play an important role in the pathogenesis of RA.