Andrographolide stimulates osteoblastogenesis and bone formation by inhibiting nuclear factor kappa-B signaling both in vivo and in vitro

Osteoporosis is a bone disease that is associated with a decrease in bone mineral density, deterioration of bone microarchitecture and increased fracture risk. Currently, available treatments mainly focus on either inhibiting osteoclast function, such as administration of bisphosphonate, calcitonin, oestrogen, selective oestrogen receptor modulator and so on, or stimulating osteoblasts, such as parathyroid hormone, to improve bone mass and skeletal microarchitecture. However, there is no option that is completely satisfactory because of the limitations of monotherapy with either class. Thus, it is highly appealing to investigate novel drugs with both antiresorptive and osteoanabolic activities that have the potential to be more beneficial than monotherapy because of the different mechanism of action. As has been proven in previous study that andrographolide (AP), as a key herbal medicine, could suppress osteoclast formation and function both in vivo and in vitro. The purpose of this present study was to identify the effect of AP on osteoblast differentiation and oestrogen deficiency - induced osteoporosis. It was concluded that AP significantly reduced oestrogen deficiency - induced bone loss in vivo. Furthermore, it was proved that tumor necrosis factor alpha severely impaired bone morphogenetic protein-2 (BMP-2)-induced osteoblast differentiation, and this inhibition could be greatly attenuated by AP. This was further supported by the fact that AP significantly increases the expression of osteoblast-specific markers, including runtrelated transcription factor-2, osteocalcin and osteopontin. In addition, molecular analysis revealed that AP greatly ceased tumor necrosis factor alpha-mediated stimulation of nuclear factor kappa-B activity, whereas overexpression of the nuclear factor kappa-B subunit p65 reversed the stimulatory effects of AP on osteoblast differentiation. Thus, combined with previous study, AP was demonstrated to be a novel agent with both antiresorptive and osteoanabolic activities and had the potential to be developed as an antiosteoporosis alternative. The translational potential of this article: This study provides strong evidence for the identification that AP has both antiresorptive and osteoanabolic activities and thus has great potential to be developed as a novel antiosteoporosis agent. (C) 2019 The Authors. Published by Elsevier (Singapore) Pte Ltd on behalf of Chinese Speaking Orthopaedic Society.