Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans
Abstract 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...
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| Format: | Article |
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Nature Publishing Group
2025-01-01
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| Series: | Bone Research |
| Online Access: | https://doi.org/10.1038/s41413-024-00382-0 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shishu Huang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-bb3d3405c72c4bc7a6b2fb8c3efc9cb6 |
| institution | Kabale University |
| issn | 2095-6231 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Bone Research |
| spelling | doaj-art-bb3d3405c72c4bc7a6b2fb8c3efc9cb62025-01-05T12:11:08ZengNature Publishing GroupBone Research2095-62312025-01-0113111610.1038/s41413-024-00382-0Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humansShishu Huang0Dashuang Gao1Zhenxia Li2Hongchen He3Xi Yu4Xuanhe You5Diwei Wu6Ze Du7Jiancheng Zeng8Xiaojun Shi9Qinshen Hu10Yong Nie11Zhong Zhang12Zeyu Luo13Duan Wang14Zhihe Zhao15Lingli Li16Guanglin Wang17Liping Wang18Zongke Zhou19Di Chen20Fan Yang21Department of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityThe 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 InstitutionsDepartment 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 DiseasesRehabilitation Medicine Center, West China Hospital, Sichuan UniversityRehabilitation Medicine Center, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan UniversityDepartment of Nursing, West China Hospital, Sichuan UniversityDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityThe 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 InstitutionsDepartment of Orthopedics Surgery and Orthopedic Research Institute, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan UniversityResearch Center for Computer-aided Drug Discovery, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesThe 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 InstitutionsAbstract 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.https://doi.org/10.1038/s41413-024-00382-0 |
| spellingShingle | 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 Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans Bone Research |
| title | Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans |
| title_full | Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans |
| title_fullStr | Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans |
| title_full_unstemmed | Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans |
| title_short | Neuronal guidance factor Sema3A inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice, monkeys and humans |
| title_sort | neuronal guidance factor sema3a inhibits neurite ingrowth and prevents chondrocyte hypertrophy in the degeneration of knee cartilage in mice monkeys and humans |
| url | https://doi.org/10.1038/s41413-024-00382-0 |
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