Baa. Scheven et al., EFFECTS OF METHOTREXATE ON HUMAN OSTEOBLASTS IN-VITRO - MODULATION BY1,25-DIHYDROXYVITAMIN D-3, Journal of bone and mineral research, 10(6), 1995, pp. 874-880
This study was designed to investigate whether methotrexate (MTX), use
d in the treatment of rheumatoid arthritis (RA), affects proliferation
and differentiation of human osteoblasts in culture, The effects of M
TX were assessed by analyzing markers of proliferation and differentia
tion of human trabecular bone-derived osteoblast-like cells cultured i
n the presence or absence of 1,25-dihydroxyvitamin D-3 (1,25 [OH]D-2(3
)). Treatment of the osteoblastic cells with MTX resulted in a strong
dose-dependent inhibition of cell proliferation with half maximal resp
onse 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)(2)D-3 to th
e cultures caused an enhanced AP expression and osteocalcin production
coinciding with a decreased osteoblast proliferation, Coincubation of
1,25(OH)(2)D-3 with MTX in doses greater than or equal to 100 nM furt
her 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)(2)D-3 cultures, In conclusion, MTX pro
ved to be a potent inhibitor of osteoblast proliferation but did not a
ffect basal osteoblastic phenotypic expression, In the presence of the
osteoblast differentiation-promotor, 1,25(OH)(2)D-3, MTX further inhi
bited cell growth which was associated with enhanced AP activity and o
steocalcin production, Thus, MTX may have profound effects on bone met
abolism and remodeling by interfering with bone cell turnover.