Reversing the imbalance in bone homeostasis via sustained release of SIRT-1 agonist to promote bone healing under osteoporotic condition  

作　　者：Wei Zhang Xingzhi Zhou Weiduo Hou Erman Chen Chenyi Ye Mo Chen Qian Lu Xiaohua Yu Weixu Li 

机构地区：[1]Department of Orthopedics,Second Affiliated Hospital,School of Medicine,Zhejiang University,310009,Hangzhou,China [2]Research Institute of Orthopaedics,Zhejiang University,310009,Hangzhou,China [3]Department of Rheumatology,Second Affiliated Hospital,School of Medicine,Zhejiang University,310009,Hangzhou,China [4]Department of Orthopedics,Huzhou Hospital,Zhejiang University,China

出　　处：《Bioactive Materials》2023年第1期429-443,共15页生物活性材料（英文）

基　　金：supported by a grant from the National Natural Science Foundation of China(No.81802221,31870959,82102597);Zhejiang Provincial Natural Science Foundation of China(LY21H070001,LQ21H060007,LY22H060006);Zhejiang Undergraduate Talent Project(No.2021R401214).

摘　　要：The imbalance of bone homeostasis is the root cause of osteoporosis.However current therapeutic approaches mainly focus on either anabolic or catabolic pathways,which often fail to turn the imbalanced bone metabolism around.Herein we reported that a SIRT-1 agonist mediated molecular therapeutic strategy to reverse the imbalance in bone homeostasis by simultaneously regulating osteogenesis and osteoclastogenesis via locally sustained release of SRT2104 from mineral coated acellular matrix microparticles.Immobilization of SRT2104 on mineral coating(MAM/SRT)harnessing their electrostatic interactions resulted in sustained release of SIRT-1 agonist for over 30 days.MAM/SRT not only enhanced osteogenic differentiation and mineralization,but also attenuated the formation and function of excessive osteoclasts via integrating multiple vital upstream signals(β-catenin,FoxOs,Runx2,NFATc1,etc.)in vitro.Osteoporosis animal model also validated that it accelerated osteoporotic bone healing and improved osseointegration of the surrounding bone.Overall,our work proposes a promising strategy to treat osteoporotic bone defects by reversing the imbalance in bone homeostasis using designated small molecule drug delivery systems.

关 键 词：Osteoporosis OSTEOBLAST OSTEOCLAST Mineral coating SIRT1 

分 类 号：R68[医药卫生—骨科学]