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Effects of methotrexate on human osteoblasts in vitro: modulation by 1,25-dihydroxyvitamin D3
- Source :
- Journal of bone and mineral research, 10(6), 874-880. Wiley-Blackwell
- Publication Year :
- 1995
-
Abstract
- This study was designed to investigate whether methotrexate (MTX), used in the treatment of rheumatoid arthritis (RA), affects proliferation and differentiation of human osteoblasts in culture. The effects of MTX were assessed by analyzing markers of proliferation and differentiation of human trabecular bone-derived osteoblast-like cells cultured in the presence or absence of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Treatment of the osteoblastic cells with MTX resulted in a strong dose-dependent inhibition of cell proliferation with half maximal response at a dose of 30 nM. MTX did not interfere with cellular alkaline phosphatase (AP) activity, the number of cells expressing cytochemical AP, or basal osteocalcin production. Addition of 1,25(OH)2D3 to the cultures caused an enhanced AP expression and osteocalcin production coinciding with a decreased osteoblast proliferation. Coincubation of 1,25(OH)2D3 with MTX in doses > or = 100 nM further inhibited osteoblast growth and induced a significant stimulation of AP expression and activity, and production of osteocalcin above the values reached in the 1,25(OH)2D3 cultures. In conclusion, MTX proved to be a potent inhibitor of osteoblast proliferation but did not affect basal osteoblastic phenotypic expression. In the presence of the osteoblast differentiation-promoter, 1,25(OH)2D3, MTX further inhibited cell growth which was associated with enhanced AP activity and osteocalcin production. Thus, MTX may have profound effects on bone metabolism and remodeling by interfering with bone cell turnover.
- Subjects :
- musculoskeletal diseases
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Osteocalcin
Radioimmunoassay
Bone and Bones
Bone remodeling
Arthritis, Rheumatoid
Calcitriol
Internal medicine
Bone cell
medicine
Humans
Orthopedics and Sports Medicine
Cells, Cultured
Analysis of Variance
Osteoblasts
Dose-Response Relationship, Drug
biology
Cell growth
Cell Differentiation
Femur Head
Osteoblast
Biological activity
Alkaline Phosphatase
Immunohistochemistry
In vitro
Methotrexate
medicine.anatomical_structure
Endocrinology
Bromodeoxyuridine
Antirheumatic Agents
biology.protein
Alkaline phosphatase
Bone Remodeling
Cell Division
Subjects
Details
- Language :
- English
- ISSN :
- 08840431
- Database :
- OpenAIRE
- Journal :
- Journal of bone and mineral research, 10(6), 874-880. Wiley-Blackwell
- Accession number :
- edsair.doi.dedup.....53bff5b29094fa54fb37e7a828aa2b09