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

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

机构地区：[1]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 [2]Branch of National Clinical Research Center for Orthopedics,Sports Medicine and Rehabilitation,Nanjing 210008,China [3]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

出　　处：《Nano Research》2024年第4期2949-2959,共11页纳米研究（英文版）

基　　金：supported by the National Key Research and Development Project(No.2021YFA1201404);Major Project of the National Natural Science Foundation of China(Nos.81991514,82272530);Jiangsu Province Medical Innovation Center of Orthopedic Surgery(No.CXZX202214);Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,Jiangsu Provincial Key Medical Talent Foundation;the Fundamental Research Funds for the Central Universities(Nos.14380493 and 14380494).

摘　　要：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 theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-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 deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关 键 词：OSTEOPOROSIS Α-CYPERONE OSTEOCLAST phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome 

分 类 号：R68[医药卫生—骨科学]