Abstract
BackgroundOsteoporosis is a worldwide severe bone disease. This study aimed to evaluate the effect of polyphyllin VII on the genesis of osteoclasts from bone marrow macrophages (BMMs) and its potentiality as a therapeutic drug for osteoporosis.MethodsBMMs were induced to differentiate into osteoclasts by RANKL and M-CSF. The cells were then treated with various concentrations of polyphyllin VII. Intracellular reactive oxygen species (ROS) measurement assay, resorption pit formation assay, tartrate-resistant acid phosphatase (TRAP) staining and TRAP activity assessment, cell viability assay, active GTPase pull-down assay, immunofluorescent staining, immunoblotting, and RT-PCR were performed.ResultsRANKL + M-CSF significantly increased TRAP activity, number of osteoclasts, number and area of lacunae, intracellular content of ROS, protein levels of Nox1, TRAF6, c-Src and p-PI3K, as well as the content of activated GTP-Rac1, which were significantly blocked by polyphyllin VII in a concentration-dependent manner.ConclusionThese findings suggested that polyphyllin VII inhibited differentiation of BMMs into osteoclasts through suppressing ROS synthesis, which was modulated by TRAF6–cSrc–PI3k signal transduction pathway including GTP-Rac1 and Nox1. Polyphyllin VII could be a therapeutic drug for osteoporosis.
Highlights
Osteoporosis is a worldwide severe bone disease
Inhibitory effect of polyphyllin VII on the mRNA expression of TRACP5, Ctsk and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) As shown in Fig. 4, gene expression of TRACP5 (Fig. 4a), Ctsk (Fig. 4b) and NFATc1 (Fig. 4c) was significantly increased in the bone marrow macrophages (BMMs) cells exposed to RANKL compared to the cells without any treatment (P < 0.05)
RANKL increased tartrate-resistant acid phosphatase (TRAP) activity, number of osteoclasts, number and area of lacunae, content of reactive oxygen species (ROS), protein levels of Nox1, TRAF6, c-Src and p-PI3K, as well as the content of activated GTP-Rac1, which were significantly blocked by polyphyllin VII in a concentration-dependent manner
Summary
Osteoporosis is a worldwide severe bone disease. Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risk of fragility fractures which represent the main clinical consequence of the disease. Fragility fractures are associated with substantial pain and suffering, disability and even death for affected patients and substantial costs to society [1]. It is estimated that approximately 40% white women with ages over 50 years old [2] and 13% white men with ages over 50 years [3] will suffer bone fractures due to osteoporosis. The main clinically applied medications for osteoporosis are bisphosphonates, estrogen, selective estrogen receptor modulators (Raloxifene), teriparatide, Denosumab, and calcitonin. Bisphosphonates, the first line medication, have the side effects of causing necrosis of jaws, severe musculoskeletal pain, esophagus cancer, and kidney failure [5]. The newly approved RANKL inhibitor, Denosumab (Prolia), inhibits the rebuild of bone, and has the risk of
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
