Methotrexate in the treatment of rheumatoid arthritis. I. In vitro effects on cells of the osteoblast lineage

• Published in: Rheumatology (Oxford, England) Vol. 41; no. 7; pp. 735 - 740
• Main Authors: Minaur, N. J., Jefferiss, C., Bhalla, A. K., Beresford, J. N.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.2002; Oxford Publishing Limited (England)
• Subjects: ADP-ribosyl Cyclase; Adult; Aged; Aged, 80 and over; Alkaline phosphatase; Alkaline Phosphatase - metabolism; Antigens, CD; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Biological and medical sciences; Biomarkers - analysis; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bones, joints and connective tissue. Antiinflammatory agents; Cell Count; Cell Division - drug effects; Cells, Cultured; CFU‐F; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Female; GPI-Linked Proteins; Humans; Male; Marrow stromal cells; Medical sciences; Membrane Glycoproteins - metabolism; Methotrexate; Methotrexate - pharmacology; Methotrexate - therapeutic use; Middle Aged; Osteoblasts; Osteoblasts - drug effects; Osteoblasts - metabolism; Pharmacology. Drug treatments; Rheumatoid arthritis; Ribs - cytology; Stem Cells - drug effects; Stromal Cells - drug effects; Stromal Cells - metabolism; STRO‐1; Human; Immunopathology; Cell culture; Cell function; Low dose; Diseases of the osteoarticular system; Autoimmune disease; Inflammatory joint disease; Proliferation; Cell differentiation; In vitro; Biological activity; Antifolate; Chemotherapy; Chronic; Treatment; Rheumatoid arthritis; Osteoblast; Immunosuppressive agent; Bone; Methotrexate
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/41.7.735

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.