Document Detail


Methotrexate (MTX) inhibits osteoblastic differentiation in vitro: possible mechanism of MTX osteopathy.
MedLine Citation:
PMID:  11246658     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To clarify the mechanism of impaired bone formation during low dose methotrexate (MTX) therapy. METHODS: The in vitro effects of MTX on the function and differentiation of osteoblastic cells were investigated using (1) a mouse osteogenic cell line (MC3T3-E1) with the capacity to differentiate into osteoblastic or osteocytes, (2) a human osteoblastic osteosarcoma cell line (SaOS-2) with a mature osteoblastic phenotype, and (3) mouse bone marrow stromal cells containing osteoblast precursors. Osteoblast function was assessed by measuring the cellular activity of alkaline phosphatase (ALP) and the mineralization capacity of cultures. RESULTS: MTX suppressed ALP activity dose-dependently in growing MC3T3-E1 cells, but proliferation of these cells was only inhibited by a high concentration of MTX. In contrast, inhibition of ALP activity in MC3T3-E1 cells of mature osteoblastic phenotype was only observed with 10(-8) M and 10(-7) M MTX, and proliferation was not influenced. ALP activity and the proliferation of SaOS-2 cells were not inhibited by MTX, even when growing cells were treated. However, both ALP activity and formation of calcified nodules in bone marrow stromal cell cultures were significantly suppressed by MTX at concentrations between l0(-10) and 10(-7) M. CONCLUSION: These results suggest that MTX suppresses bone formation by inhibiting the differentiation of early osteoblastic cells.
Authors:
R Uehara; Y Suzuki; Y Ichikawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of rheumatology     Volume:  28     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-03-14     Completed Date:  2001-06-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  251-6     Citation Subset:  IM    
Affiliation:
Department of Rheumatic and Allergic Diseases, St Marianna University School of Medicine, Kawasaki, Japan.
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MeSH Terms
Descriptor/Qualifier:
Alkaline Phosphatase / drug effects,  metabolism
Animals
Arthritis, Rheumatoid / drug therapy
Bone Marrow Cells / drug effects,  enzymology,  pathology
Bone and Bones / drug effects*,  pathology,  physiopathology
Calcification, Physiologic / drug effects,  physiology
Cell Differentiation / drug effects*,  physiology
Dose-Response Relationship, Drug
Humans
Methotrexate / toxicity*
Mice
Osteoblasts / drug effects*,  enzymology,  pathology
Tumor Cells, Cultured / drug effects,  enzymology,  pathology
Chemical
Reg. No./Substance:
59-05-2/Methotrexate; EC 3.1.3.1/Alkaline Phosphatase

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