Selenium nanoparticles functionalized by mushroom polysaccharide-protein complex: A novel nano-mineral for managing postmenopausal osteoporosis

With an increase in aging population, osteoporosis has become one of the major public health issues nowadays, affecting over 200 million people worldwide. Since current medications are associated with various side effects, there is a clear clinical need to develop alternative therapeutics for managing osteoporosis. Selenium is an essential trace mineral, which has been proved to play important role in bone health. However, the narrow therapeutic window of selenium has greatly hindered its further development. Recently, selenium nanoparticles (SeNPs) have become a new selenium source due to its promising bioactivity and low toxicity. Nevertheless, scientific research concerning their effects on bone health is still very limited. By using the mushroom polysaccharide-protein complex isolated from Cordyceps sinensis, we have successfully prepared novel SeNPs (“Cs4-SeNPs”) with well-characterized structure and high stability. Interestingly, Cs4-SeNPs (10 μM) were found to markedly induce proliferation, differentiation, and mineralization of the pre-osteoblast murine MC3T3-E1 cells. Further mechanistic study discovered that after cellular internalization via endocytosis, Cs4-SeNPs would trigger Nox4-derived intracellular ROS generation in the MC3T3-E1 cells followed by promoting downstream BMP-2 gene transcription and activating BMP signaling via both Smad dependent and Smad independent p38 MAPK pathways. More importantly, Cs4-SeNPs (25–500 μg/kg BW/d) exhibitedpromising in vivo bone protective efficacy against OVX-induced osteoporosis by promoting bone formation, inhibiting bone resorption, and improving bone microarchitecture after oral gavage for 6 weeks. Findings of this study collectively suggested that Cs4-SeNPs is of great potential to be further developed into a safe and evidence-based nano-mineral for managing postmenopausal osteoporosis.