首页|Liposomal α-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

Liposomal α-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported the α-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system of α-CYP,that specifically targets the bone resorption interface.Firstly,we found that the α-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliver α-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated that α-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded with α-CYP might provide a novel and effective strategy to treat osteoporosis.

osteoporosisα-cyperoneosteoclastphosphoinositide 3-kinase/protein kinase B(PI3K/Akt)liposome

Lin Yang、Xueying An、Wang Gong、Wenshu Wu、Bin Liu、Xiaoyan Shao、Yansi Xian、Rui Peng、Baosheng Guo、Qing Jiang

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Division of Sports Medicine and Adult Reconstructive Surgery,Department of Orthopedic Surgery,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University,321 Zhongshan Road,Nanjing 210008,China

Branch of National Clinical Research Center for Orthopedics,Sports Medicine and Rehabilitation,Nanjing 210008,China

State Key Laboratory of Pharmaceutical Biotechnology,Medical School,Nanjing University & Division of Sports Medicine and Adult Reconstructive Surgery,Department of Orthopedic Surgery,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China

State Key Laboratory of Pharmaceutical Biotechnology,Medical School,Nanjing University & Division of Sports Medicine and Adult Reconstructive Surgery,Department of Orthopedic Surgery,Nanj

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National Key Research and Development ProjectMajor Project of the National Natural Science Foundation of ChinaMajor Project of the National Natural Science Foundation of ChinaJiangsu Province Medical Innovation Center of Orthopedic SurgeryJiangsu Provincial Key Medical Center FoundationJiangsu Provincial Medical Outstanding Talent FoundationJiangsu Provincial Medical Youth Talent FoundationJiangsu Provincial Key Medical Talent FoundationFundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities

2021YFA12014048199151482272530CXZX2022141438049314380494

2024

10.1007/s12274-023-6224-7

纳米研究(英文版)

纳米研究(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.17(4)
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