Abstract

Osteoporosis is an enormous health problem caused by the imbalance between bone resorption and bone formation. The current therapeutic strategies for osteoporosis still have some limitations. Boldine, an alkaloid isolated from Peumus boldus, has been shown to have antioxidant and anti-inflammatory effects in vivo. For the first time, we discover that boldine has a protective effect for the estrogen deficiency-induced bone loss in mice. According to the Micro-CT and histomorphometry assays, boldine conducts this protective effect through inhibiting bone resorption without affecting bone formation in vivo. Moreover, we showed that boldine can inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation via impairing the AKT signaling pathways, while SC79 (an AKT agonist) partially rescue this effect. In conclusion, our results suggest that boldine can prevent estrogen deficiency-induced osteoporosis by inhibiting osteoclastogenesis. Thus, boldine may be served as a novel therapeutic agent for anti-osteoporotic therapy.

Highlights

  • Osteoporosis is one of several major health problems, affecting 10 million people in the United States and 27.6 million in the Europe (Zhou et al, 2018)

  • To explore the effect of boldine on osteoporosis, we used a murine model of OVX-induced osteoporosis. 8-week-old female wide type mice were randomly divided into three groups: Sham (Sham + Vehicle), OVX (OVX + Vehicle), and Boldine (OVX + Boldine)

  • OVX group showed dramatic bone loss compared to the Sham group, as revealed by decreased bone mineral density (BMD), trabecular bone bone volume/total volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), increased structural model index (SMI) and trabecular separation (Tb.Sp) (Figures 1F–L)

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Summary

Introduction

Osteoporosis is one of several major health problems, affecting 10 million people in the United States and 27.6 million in the Europe (Zhou et al, 2018). It is induced by the imbalance between bone formation and bone resorption NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001). This imbalance results in decreased bone mass and abnormal bone architecture, increasing the risk of fragility fracture (Canalis et al, 2007). The preventions and treatments of this disease are of significant importance

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