Combination of alendronate and genistein synergistically suppresses osteoclastic differentiation of RAW267.4 cells in vitro

Abstract

Abstract. Bone is a dynamic tissue that undergoes constant remodeling, with removal by osteoclastic bone resorption and replacement via osteoblastic bone formation and mineralization. Deterioration of bone mass with aging leads to osteoporosis. Bisphosphonates are potent inhibitors of osteoclastic bone resorption. Genistein, an isoflavone, exerts a bone anabolic effect by suppressing osteoclastic bone resorption and stimulating osteoblastic bone formation. The present study was undertaken to investigate the anabolic effects of a combination of alendronate and genistein on osteoclastic differentiation. Preosteoclastic RAW267.4 cells were cultured with alendronate (0.1-100 µM) and/or genistein (0.1-100 µM) in vitro. Alendronate or genistein alone had no significant effect on the proliferation and death of RAW267.4 cells. Notably, the combination of the two agents was found to potently and synergistically repress the proliferation and death of RAW267.4 cells. Moreover, alendronate or genistein used separately at higher concentrations suppressed the osteoclastic differentiation of RAW267.4 cells induced by receptor activator of nuclear factor-κB ligand (RANKL) in vitro. However, combinations of the two agents (0.1-100 µM) synergistically suppressed the RANKL-induced osteoclastic differentiation. In conclusion, bisphosphonate and genistein combination therapy may provide a novel strategy for the prevention and treatment of osteoclastic bone resorption.

Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo

“…As a representative example, genistein as botanical isoflavone are contained at relatively high concentrations in soybean. Genistein has suppressive effects on the osteoclastic differentiation of preosteoclastic RAW 264.7 cells in vitro [ 13 ]. Furthermore, genistein inhibits the bone loss induced by ovariectomized mice [ 14 ] and improved the quality of life and depression symptoms in osteopenic postmenopausal women [ 15 , 16 ].…”

The protective activity of genistein against bone and cartilage diseases

“…In pre-osteoclastic RAW 264.7 cells, genistein can decrease RANKL-induced osteoclastic differentiation in vitro . Furthermore, genistein may synergize with bisphosphonate alendronate to inhibit the osteoclastic differentiation induced by RANKL, which providing a novel strategy for clinic prevention and treatment of osteoporosis ( Yamaguchi and Levy, 2017 ) ( Table 1 ). Genistein also limits the generation of ROS by up regulation of NRF2/HO-1 signaling pathway, down regulation of NADPH oxidase 1 (NOX1), and inhibition of disrupting the mitochondrial electron transport chain system in RANKL-treated RAW264.7 cells ( Lee et al, 2014 ).…”

Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis

“…Furthermore, a positive effect on bone was obtained through enhanced osteoblastic differentiation and maturation via the activation of ER (estrogen receptor), p38 MAPK–Runx2, and NO/cGMP pathways [ 60 , 61 , 62 ]. It also inhibited osteoclast formation and bone resorption by inducing the osteoclastogenic inhibitor osteoprotegerin (OPG) and by blocking NF-κB signaling [ 60 , 63 ].…”