Shiyin Xu , Zixuan Zhang , Xiaolei Zhou , Yuxiao Liao , Zhao Peng , Zitong Meng , Andreas K. Nüssler , Liang Ma , Hui Xia , Liegang Liu , Wei Yang
{"title":"狗气源性纳米囊泡(GqDNVs)促进MC3T3-E1细胞增殖,促进骨折愈合","authors":"Shiyin Xu , Zixuan Zhang , Xiaolei Zhou , Yuxiao Liao , Zhao Peng , Zitong Meng , Andreas K. Nüssler , Liang Ma , Hui Xia , Liegang Liu , Wei Yang","doi":"10.1016/j.phymed.2025.156755","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div><em>Lycium barbarum</em> L., also known as Gouqi, a traditional Chinese herbal medicine, is widely utilized in health care products and clinical therapies. Its muscle and bone strengthening efficacy has been recorded in medical classics for a long time. In addition, plant exosome-like nanovesicles (PELNVs) have attracted more and more attention owing to their biological traits. Therefore, we intended to explore the functions, regulatory role, and underlying mechanism of Gouqi-derived Nanovesicles (GqDNVs) on fracture healing.</div></div><div><h3>Methods</h3><div>In this study, we employed the sucrose density gradient differential ultracentrifugation to isolate GqDNVs. The effects of GqDNVs on the proliferation and differentiation of MC3T3-E1 cells were evaluated using the CCK-8 assay, ALP activity measurement, and cell scratch assay. Additionally, leveraging a fracture mouse model, we utilized Micro-CT, immunological staining, and histologic analyses to comprehensively assess the impact of GqDNVs on fracture healing in mice.</div></div><div><h3>Results</h3><div>GqDNVs stimulated cell viability, increased ALP activity, and promoted cellular osteogenic protein expression (OPN, ALP, and RUNX2). Subsequently, in the mouse fracture model, trabecular thickness, and bone marrow density were increased in the GqDNVs treatment group after 28 days of injection. Meanwhile, the expressions of OPN and BGP were significantly elevated after both 14 and 28 days. Additionally, the expressions of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, p-4EBP1/4EBP1 and p-p70S6K/ p70S6K were also increased after14 days of treatment.</div></div><div><h3>Conclusions</h3><div>GqDNVs effectively promoted the proliferation and differentiation of MC3T3-E1 cells. Furthermore, GqDNVs could improve fracture healing, which is associated with PI3K/Akt/mTOR/p70S6K/4EBP1 signaling pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156755"},"PeriodicalIF":6.7000,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Gouqi-derived Nanovesicles (GqDNVs) Promoted MC3T3-E1 Cells Proliferation and Improve Fracture Healing\",\"authors\":\"Shiyin Xu , Zixuan Zhang , Xiaolei Zhou , Yuxiao Liao , Zhao Peng , Zitong Meng , Andreas K. Nüssler , Liang Ma , Hui Xia , Liegang Liu , Wei Yang\",\"doi\":\"10.1016/j.phymed.2025.156755\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div><em>Lycium barbarum</em> L., also known as Gouqi, a traditional Chinese herbal medicine, is widely utilized in health care products and clinical therapies. Its muscle and bone strengthening efficacy has been recorded in medical classics for a long time. In addition, plant exosome-like nanovesicles (PELNVs) have attracted more and more attention owing to their biological traits. Therefore, we intended to explore the functions, regulatory role, and underlying mechanism of Gouqi-derived Nanovesicles (GqDNVs) on fracture healing.</div></div><div><h3>Methods</h3><div>In this study, we employed the sucrose density gradient differential ultracentrifugation to isolate GqDNVs. The effects of GqDNVs on the proliferation and differentiation of MC3T3-E1 cells were evaluated using the CCK-8 assay, ALP activity measurement, and cell scratch assay. Additionally, leveraging a fracture mouse model, we utilized Micro-CT, immunological staining, and histologic analyses to comprehensively assess the impact of GqDNVs on fracture healing in mice.</div></div><div><h3>Results</h3><div>GqDNVs stimulated cell viability, increased ALP activity, and promoted cellular osteogenic protein expression (OPN, ALP, and RUNX2). Subsequently, in the mouse fracture model, trabecular thickness, and bone marrow density were increased in the GqDNVs treatment group after 28 days of injection. Meanwhile, the expressions of OPN and BGP were significantly elevated after both 14 and 28 days. Additionally, the expressions of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, p-4EBP1/4EBP1 and p-p70S6K/ p70S6K were also increased after14 days of treatment.</div></div><div><h3>Conclusions</h3><div>GqDNVs effectively promoted the proliferation and differentiation of MC3T3-E1 cells. Furthermore, GqDNVs could improve fracture healing, which is associated with PI3K/Akt/mTOR/p70S6K/4EBP1 signaling pathway.</div></div>\",\"PeriodicalId\":20212,\"journal\":{\"name\":\"Phytomedicine\",\"volume\":\"142 \",\"pages\":\"Article 156755\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2025-04-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Phytomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0944711325003940\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944711325003940","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Lycium barbarum L., also known as Gouqi, a traditional Chinese herbal medicine, is widely utilized in health care products and clinical therapies. Its muscle and bone strengthening efficacy has been recorded in medical classics for a long time. In addition, plant exosome-like nanovesicles (PELNVs) have attracted more and more attention owing to their biological traits. Therefore, we intended to explore the functions, regulatory role, and underlying mechanism of Gouqi-derived Nanovesicles (GqDNVs) on fracture healing.
Methods
In this study, we employed the sucrose density gradient differential ultracentrifugation to isolate GqDNVs. The effects of GqDNVs on the proliferation and differentiation of MC3T3-E1 cells were evaluated using the CCK-8 assay, ALP activity measurement, and cell scratch assay. Additionally, leveraging a fracture mouse model, we utilized Micro-CT, immunological staining, and histologic analyses to comprehensively assess the impact of GqDNVs on fracture healing in mice.
Results
GqDNVs stimulated cell viability, increased ALP activity, and promoted cellular osteogenic protein expression (OPN, ALP, and RUNX2). Subsequently, in the mouse fracture model, trabecular thickness, and bone marrow density were increased in the GqDNVs treatment group after 28 days of injection. Meanwhile, the expressions of OPN and BGP were significantly elevated after both 14 and 28 days. Additionally, the expressions of p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR, p-4EBP1/4EBP1 and p-p70S6K/ p70S6K were also increased after14 days of treatment.
Conclusions
GqDNVs effectively promoted the proliferation and differentiation of MC3T3-E1 cells. Furthermore, GqDNVs could improve fracture healing, which is associated with PI3K/Akt/mTOR/p70S6K/4EBP1 signaling pathway.
期刊介绍:
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.