Osteoarthritis is a multifactorial disease characterized by loss of articular cartilage
and subchondral plate thickening. Therefore, biochemical analysis of the underlying
bone tissue has provided important information for treatment of osteoarthritis. In
this study, we determined the potential role of formononetin, a phytoestrogen isolated
from Astragalus membranaceus to alter the expression of metabolic markers and cytokine
production of human normal osteoblasts (Obs) and osteoarthritis subchondral osteoblasts
(OA Obs). Human OA Obs and normal Obs were cultured for 3days, 7days or 14days in
the present medium only or were treated with various doses of formononetin. Cells
were analyzed for viability by WST-8 assay, alkaline phosphatase (ALP) activity, osteogenic
markers (osteocalcin (OCN) and type I collagen (Col I)) and cytokines (interleukin-6
(IL-6), vascular endothelial growth factor (VEGF), bone morphogenic protein-2 (BMP-2)).
The level of IL-6, VEGF, BMP-2, OCN and Col I was increased in OA Obs compared with
normal Obs. Formononetin dose-dependently decreased ALP, IL-6, VEGF, BMP-2, OCN and
Col I in OA Obs, while markedly increased ALP, VEGF, BMP-2, OCN and Col I in normal
Obs. Interestingly, formononetin markedly increased the expression of VEGF and BMP-2
for 3days of culture and significantly increased OCN and Col I at 14days in human
normal Obs. The remodeling effect of formononetin on osteogenic markers and cytokines
of inflammatory mediators was more striking in OA Obs as well. Taken together, these
results could suggest that formononetin has biphasic positive effects on normal Obs
and OA Obs by modifying their biological synthetic capacities.
Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.