Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice,monkeys and humans  

作　　者：Shishu Huang Dashuang Gao Zhenxia Li Hongchen He Xi Yu Xuanhe You Diwei Wu Ze Du Jiancheng Zeng Xiaojun Shi Qinshen Hu Yong Nie Zhong Zhang Zeyu Luo Duan Wang Zhihe Zhao Lingli Li Guanglin Wang Liping Wang Zongke Zhou Di Chen Fan Yang 

机构地区：[1]Department of Orthopedics Surgery and Orthopedic Research Institute,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu,China [2]The Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,CAS Key Laboratory of Brain Connectome and Manipulation,the Brain Cognition and Brain Disease Institute(BCBDI),Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions,Shenzhen,China [3]University of Chinese Academy of Sciences,Beijing,China [4]The seventh Clinical Medical School of Guangzhou University of Chinese Medicine,Bao’an District TCM Hospital,Shenzhen,Guangdong,China [5]Department of Orthodontics,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,College of Stomatology,Shanghai Jiao Tong University,National Center for Stomatology,National Clinical Research Center for Oral Diseases,Shanghai,China [6]Rehabilitation Medicine Center,West China Hospital,Sichuan University,Chengdu,China [7]State Key Laboratory of Oral Diseases,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,China [8]Department of Nursing,West China Hospital,Sichuan University,Chengdu,China [9]Research Center for Computer-aided Drug Discovery,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,China

出　　处：《Bone Research》2025年第1期75-90,共16页骨研究(英文版)

基　　金：partly National Key R&D Program of China(2023YFA1801200,2023YFA1801202);Major Program of the National Natural Science Foundation of China(T2394532);National Natural Science Foundation of China(82072489);The Foundation of Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019007);Shenzhen Medical Research Fund(B2302011);The Sanming Project of Medicine in Shenzhen(SZZYSM202311013);The China Postdoctoral Science Foundational,2023M743679;Shenzhen Science and Technology Research Funding(JCYJ20220818101414032);Key Research Project of Science&Technology Department of Sichuan Province,China(2024YFFK0041)。

摘　　要：Osteoarthritis(OA)is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms.Normal articular cartilage maintains at aneural state.Neuron guidance factor Semaphorin 3A(Sema3A)is a membrane-associated secreted protein with chemorepulsive properties for axons.However,the role of Sema3A in articular cartilage is still not clear.In the present studies,we investigated the functions of Sema3A in OA development in mice,non-human primates,and patients with OA.Sema3A has a protective effect on cartilage degradation,validated by the organoid culture in vitro and confirmed in chondrocyte-specific Sema3A conditional knockout mice.We demonstrated that Sema3A is a key molecule in maintaining cartilage homeostasis from chondrocyte hypertrophy via activating the PI3K pathway.The potential usage of Sema3A for OA treatment was validated in mouse and Rhesus macaque OA models through intra-articular injection of Sema3A,and also in patients by administering Sema3A containing platelet-rich plasma into the knee joints.Our studies demonstrated that Sema3A exerts a critical role in inhibiting neurite ingrowth and preventing chondrocyte hypertrophy in cartilage,and could be potentially used for OA treatment.

关 键 词：SEMA3A CARTILAGE HYPERTROPHY 

分 类 号：R54[医药卫生—心血管疾病]