首页|Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization

Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization

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Alveolar bone regeneration has been strongly linked to macrophage polarization.M1 macrophages aggravate alveolar bone loss,whereas M2 macrophages reverse this process.Berberine(BBR),a natural alkaloid isolated and refined from Chinese medicinal plants,has shown therapeutic effects in treating metabolic disorders.In this study,we first discovered that culture supernatant(CS)collected from BBR-treated human bone marrow mesenchymal stem cells(HBMSCs)ameliorated periodontal alveolar bone loss.CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro.To clarify the underlying mechanism,the bioactive materials were applied to different animal models.We discovered macrophage colony-stimulating factor(M-CSF),which regulates macrophage polarization and promotes bone formation,a key macromolecule in the CS.Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats.Colony-stimulating factor 1 receptor(CSF1R)inhibitor or anti-human M-CSF(M-CSF neutralizing antibody,Nab)abolished the therapeutic effects of the CS of BBR-treated HBMSCs.Moreover,AKT phosphorylation in macrophages was activated by the CS,and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab.These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis.Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets.Overall,our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

berberinehuman bone marrow mesenchymal stem cellsalveolar bone regenerationmacrophage colony-stimulating factorAKT phosphorylation

Ziyue Qin、Yanxing Han、Yifei Du、Yixuan Zhang、Yifeng Bian、Ruyu Wang、Haoran Wang、Fanyi Guo、Hua Yuan、Yongchu Pan、Jianliang Jin、Qigang Zhou、Yuli Wang、Feng Han、Yan Xu、Jiandong Jiang

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Department of Oral and Maxillofacial Surgery,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing 210029,China

Jiangsu Province Key Laboratory of Oral Diseases,Nanjing Medical University,Nanjing 210029,China

Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing 210029,China

State Key Laboratory of Bioactive Substances and Function of Natural Medicine,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

Gusu school,Nanjing medical university,Suzhou 215002,China

Key Laboratory of Cardiovascular & Cerebrovascular Medicine,Drug Target and Drug Discovery Center,School of Pharmacy,Nanjing Medical University,Nanjing 211166 China

Department of Orthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing 210029,China

Department of Human Anatomy,Research Centre for Bone and Stem Cells,Key Laboratory for Aging & Disease,The State Key Laboratory of Reproductive Medicine,Nanjing Medical University,Nanjing 211166,China

Department of Clinical Pharmacology,School of Pharmacy,Nanjing Medical University,Nanjing Jiangsu,211166,China

Department of Periodontology,The Affiliated Stomatological Hospital of Nanjing Medical University,Nanjing 210029,China

Department of Virology,Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

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CAMS Innovation Foundation for Medical SciencesPriority Academic Program Development of Jiangsu Higher Education InstitutionsJiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital CuJiangsu Provincial Medical Innovation Center

2016-12M-1-0112018-87YJXYYJSDW4CXZX202227

2024

10.1007/s11427-023-2454-9

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(5)