Department of Food and Nutrition, Andong National University, Andong 36729, South Korea; Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, South Korea.
Department of Food and Nutrition, Andong National University, Andong 36729, South Korea; Department of Molecular Medicine, CMRI, School of Medicine, Kyungpook National University, Daegu, South Korea.
J Control Release. 2023 Mar;355:184-198. doi: 10.1016/j.jconrel.2023.01.071. Epub 2023 Feb 6.
Plants-releasing exosome-like nanovesicles (PENs) contain miRNA, bioactive lipids, mRNAs, and proteins to exert antioxidant, anti-inflammatory, and regenerative activity. Substances extracted from yams have been reported to promote osteoblast growth in bone regeneration, which prevent weak and brittle bones in osteoporosis. Herein, we describe the beneficial effects of yam-derived exosome-like nanovesicles (YNVs) on promoting differentiation and mineralization of osteoblasts for bone regeneration in ovariectomized (OVX)-induced osteoporotic mice. YNVs were successfully isolated and characterized. YNVs stimulate the proliferation, differentiation, and mineralization of osteoblasts with increased bone differentiation markers (OPN, ALP, and COLI). Interestingly, YNVs do not contain saponins including diosgenin and dioscin known to mainly exert osteogenic activity of yams. Instead, the osteogenic activity of YNVs was revealed to be resulted from activation of the BMP-2/p-p38-dependent Runx2 pathway. As a result, YNVs promote longitudinal bone growth and mineral density of the tibia in the OVX-induced osteoporotic mice in vivo, and these results positively correlate the significant increases in osteoblast-related parameters. In addition, the orally administered YNVs were transported through the GI tract and absorbed through the small intestine. These results showed an excellent systemic biosafety determined by histological analysis and liver/kidney toxicity tests. Taken together, YNVs can serve as a safe and orally effective agent in the treatment of osteoporosis.
植物来源的外泌体样纳米囊泡（PENs）包含 miRNA、生物活性脂质、mRNA 和蛋白质，具有抗氧化、抗炎和再生作用。从山药中提取的物质已被报道可促进成骨细胞在骨再生中的生长，从而预防骨质疏松症中骨骼脆弱和易碎。在此，我们描述了山药来源的外泌体样纳米囊泡（YNVs）在促进破骨细胞分化和矿化以用于去卵巢诱导的骨质疏松症小鼠骨再生中的有益作用。成功分离和表征了 YNVs。YNVs 刺激成骨细胞的增殖、分化和矿化，增加了骨分化标志物（OPN、ALP 和 COLI）。有趣的是，YNVs 不包含薯蓣皂苷元（diosgenin）和薯蓣皂苷（dioscin）等皂角苷，这些皂角苷主要发挥山药的成骨活性。相反，YNVs 的成骨活性被揭示是由于 BMP-2/p-p38 依赖性 Runx2 通路的激活。结果，YNVs 促进了去卵巢诱导的骨质疏松症小鼠体内胫骨的纵向骨生长和骨密度，并且这些结果与成骨细胞相关参数的显著增加呈正相关。此外，口服给予的 YNVs 通过胃肠道转运，并被小肠吸收。这些结果通过组织学分析和肝/肾毒性测试表明具有良好的全身生物安全性。总之，YNVs 可作为治疗骨质疏松症的安全有效口服药物。
