Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit  

作　　者：Ruyu Wang Tianxiao Wang Ziyu Chen Jiandong Jiang Yifei Du Hua Yuan Yongchu Pan Yuli Wang 

机构地区：[1]Department of Oral and Maxillofacial Surgery,The Affiliated Stomatological Hospitalof Nanjing Medical University,State Key LaboratoryCultivation Baseof Research,Prevention and Treatment for Oral Diseases,Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine,Nanjing Medical University,Nanjing 210029,China [2]Department of Stomatology,Chongzhou People's Hospital,Chengdu 611230,China [3]Medical Basic Research Innovation Centre for Cardiovascular and Cerebrovascular Diseases,Ministry of Education International Joint Laboratory for Drug Target of Criticallnesses,School of Pharmacy,Nanjing Medical University,Nanjing 211166,China [4]Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China [5]Department of Orthodontic,The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Baseof Research,Prevention and Treatment for Oral Diseases,Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine,Nanjing Medical University,Nanjing 210029,China

出　　处：《Science China(Life Sciences)》2025年第4期1025-1041,共17页中国科学(生命科学英文版)

基　　金：supported by grants from the Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4);Jiangsu Provincial Medical Innovation Center(CXZX202227)。

摘　　要：Delayed tooth extraction socket(TES)healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients.Excessive amounts of M1 macrophages,apoptotic neutrophils(ANs),and neutrophil extracellular traps(NETs)impair alveolar bone regeneration during TES healing.In the present study,we first discovered that conditioned medium(CM)collected from berberine-treated human bone marrow mesenchymal stem cells(BBR-HB-CM)accelerated TES healing.BBR-HB-CM contained bioactive materials that promoted the polarization of macrophages from M1 to M2,impeded the formation of ANs and NETs,and modulated M2 macrophage efferocytosis in vivo and in vitro.Mechanistically,BBR-HB-CM promoted bone formation by inhibiting macrophage-myofibroblast transition and reprogrammed macrophage polarization through p85/AKT/mTOR pathway-dependent autophagy.The 3-methyladenine abolished the therapeutic effects of BBR-HB-CM.Further studies revealed that BBR-HB-CM accelerated TES healing in rats with type 2 diabetes mellitus.Overall,our results demonstrated that BBR-HB-CM had high potential to promote rapid TES healing.

关 键 词：BERBERINE human bone marrow mesenchymal stem cells tooth extraction socket macrophages apoptotic neutrophils neutrophil extracellular traps 

分 类 号：R78[医药卫生—口腔医学]