PDF(Pubmed)
Abstract：
Although various anti-osteoporosis drugs are available, the limitations of these therapies, including drug resistance and collateral responses, require the development of novel anti-osteoporosis agents. Rhizoma Drynariae displays a promising anti-osteoporosis effect, while the effective component and mechanism remain unclear. Here, we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles (RDNVs) for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) by targeting estrogen receptor-alpha (ERα). RDNVs, a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation, exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model. RDNVs, effectively internalized by hBMSCs, enhanced proliferation and ERα expression levels of hBMSC, and promoted osteogenic differentiation and bone formation. Mechanistically, via the ERα signaling pathway, RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs, which are involved in regulating osteogenic differentiation. Further analysis revealed that naringin, existing in RDNVs, was the active component targeting ERα in the osteogenic effect. Taken together, our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.
摘要：
虽然有各种抗骨质疏松药物，这些疗法的局限性，包括耐药性和附带反应，需要开发新的抗骨质疏松药物。骨碎补显示出有希望的抗骨质疏松作用，而有效成分和机制尚不清楚。这里,我们揭示了骨碎补来源的纳米囊泡(RDNVs)治疗绝经后骨质疏松症的潜力,并证明RDNVs通过靶向雌激素受体α(ERα)增强人骨髓间充质干细胞(hBMSCs)的成骨分化.RDNV,一种通过差异超速离心从新鲜骨碎补根汁中分离出的天然产物，在卵巢切除的小鼠模型中表现出有效的骨组织靶向活性和抗骨质疏松症功效。RDNV,被hBMSCs有效内化，增强hBMSC的增殖和ERα表达水平，并促进成骨分化和骨形成。机械上,通过ERα信号通路，RDNVs促进hBMSCs中骨形态发生蛋白2和runt相关转录因子2的mRNA和蛋白表达,参与调节成骨分化。进一步的分析表明，柚皮苷，存在于RDNV中，是成骨作用中靶向ERα的活性成分。一起来看,我们的研究发现,RDNVs中的柚皮苷通过雌激素样作用促进hBMSCs增殖和成骨分化,从而表现出令人兴奋的骨组织靶向活性,逆转骨质疏松.
