文献类型：期刊文献

英文题名：Harmine Alleviates Titanium Particle-Induced Inflammatory Bone Destruction by Immunomodulatory Effect on the Macrophage Polarization and Subsequent Osteogenic Differentiation

作者：Wang, Liangliang[1];Wang, Qing[2];Wang, Wei[2];Ge, Gaoran[2];Xu, Nanwei[1];Zheng, Dong[1];Jiang, Shijie[1];Zhao, Gongyin[1];Xu, Yaozeng[2];Wang, Yuji[1,3,4,5];Zhu, Ruixia[1];Geng, Dechun[2]

第一作者：Wang, Liangliang

通信作者：Wang, YJ[1];Zhu, RX[1];Geng, DC[2];Wang, YJ[3];Wang, YJ[4];Wang, YJ[5]

机构：[1]Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Dept Orthopaed, Changzhou, Jiangsu, Peoples R China;[2]Soochow Univ, Affiliated Hosp 1, Dept Orthopaed, Suzhou, Peoples R China;[3]Mayo Clin, Dept Orthoped Surg, Rochester, MN USA;[4]Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA;[5]Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, Baiyin, Peoples R China

第一机构：Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Dept Orthopaed, Changzhou, Jiangsu, Peoples R China

通信机构：[1]corresponding author), Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Dept Orthopaed, Changzhou, Jiangsu, Peoples R China;[2]corresponding author), Soochow Univ, Affiliated Hosp 1, Dept Orthopaed, Suzhou, Peoples R China;[3]corresponding author), Mayo Clin, Dept Orthoped Surg, Rochester, MN USA;[4]corresponding author), Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA;[5]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp 3, Dept Orthoped, Baiyin, Peoples R China.|[10735]甘肃中医药大学;

年份：2021

卷号：12

外文期刊名：FRONTIERS IN IMMUNOLOGY

收录：;Scopus(收录号：2-s2.0-85107028044);WOS:【SCI-EXPANDED(收录号:WOS:000656134900001)】；

基金：This research was supported by the National Natural Science Foundation of China (82002321, 82072425, 81873991), the Social Development Project of Jiangsu Province (BE2015632). the Jiangsu Provincial Medical Youth Talent (QNRC2016751), the Natural Science Foundation of Jiangsu province (BK20180001), and Special Project of Diagnosis and Treatment for Clinical Diseases of Suzhou (LCZX202003).

语种：英文

外文关键词：peri-prosthetic osteolysis; chronic inflammation; harmine; macrophage polarization; osteoimmunomodulatory

摘要：Peri-prosthetic osteolysis (PPO) and following aseptic loosening are regarded as the prime reasons for implant failure after joint replacement. Increasing evidence indicated that wear-debris-irritated inflammatory response and macrophage polarization state play essential roles in this osteolytic process. Harmine, a beta-carboline alkaloid primitively extracted from the Peganum harmala seeds, has been reported to have various pharmacological effects on monoamine oxidase action, insulin intake, vasodilatation and central nervous systems. However, the impact of harmine on debris-induced osteolysis has not been demonstrated, and whether harmine participates in regulating macrophage polarization and subsequent osteogenic differentiation in particle-irritated osteolysis remains unknown. In the present study, we investigated the effect of harmine on titanium (Ti) particle-induced osteolysis in vivo and in vitro. The results suggested harmine notably alleviated Ti particle-induced bone resorption in a murine PPO model. Harmine was also found to suppress the particle-induced inflammatory response and shift the polarization of macrophages from M1 phenotypes to M2 phenotypes in vivo and in vitro, which improved anti-inflammatory and bone-related cytokines levels. In the conditioned medium from Ti particle-stimulated murine macrophage RAW264.7 cells treated with harmine, the osteoblast differentiation ability of mouse pre-osteoblastic MC3T3-E1 cells was greatly increased. And we also provided evidences that the immunomodulatory capacity of harmine might be attributed to the inhibition of the c-Jun N-terminal kinase (JNK) in wear particle-treated macrophages. All the results strongly show that harmine might be a promising therapeutic agent to treat PPO.