Rheumatology 2002; 41: 735-740
© 2002 British Society for Rheumatology
Original Papers |
Methotrexate in the treatment of rheumatoid arthritis. I. In vitro effects on cells of the osteoblast lineage
Bone Research Group, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY and
1 The Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK
Objective. Low-dose methotrexate (MTX) is often used in the treatment of rheumatoid arthritis (RA). To be effective, treatment must be long-term, and there are concerns that MTX may impair bone formation in a population already predisposed to osteoporosis. The purpose of this investigation was to determine the direct effects of MTX at clinically relevant doses on the growth and differentiation of human cells of the osteoblast (bone-forming) lineage.
Methods. Cells derived from the marrow stroma (BMSC) and trabecular surfaces [human bone-derived cells (HBDC)] of adult ribs were cultured in the absence or presence of MTX (1–1000 nM). To promote the differentiation and further maturation of cells of the osteoblast lineage, one half of the cultures were treated additionally with 10 nM dexamethasone (Dx).
Results. In cultures of BMSC, treatment with MTX (±Dx) did not affect the total number of colonies that formed or the expression of the developmental markers STRO-1 and alkaline phosphatase (AP). At concentrations 
10 nM, however, there was a statistically significant reduction in the number of cells harvested at the end of primary culture. In cultures of HBDC, treatment with MTX (in the presence of Dx) did not affect cell number or the expression of AP.
Conclusions. At concentrations 10 nM, treatment with MTX inhibits the proliferation of primitive marrow stromal cells, but not their ability to undergo osteogenic differentiation. The proliferation and further maturation of cells of the osteoblast lineage is not affected by treatment with MTX. These findings are reassuring for clinicians using MTX in the treatment of RA.
KEY WORDS: Rheumatoid arthritis, Methotrexate, CFU-F, Marrow stromal cells, Osteoblasts, STRO-1, Alkaline phosphatase.
Correspondence to: N. J. Minaur, 66 Third Avenue, Bath BA2 3NZ, UK.
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