文献类型：期刊文献

英文题名：Magnesium Ions Promote the Induction of Immunosuppressive Bone Microenvironment and Bone Repair through HIF-1α-TGF-β Axis in Dendritic Cells

作者：Dai, Yuya[1];Wu, Jinhui[1];Wang, Junyou[2];Wang, Haoze[3];Guo, Bingqing[4];Jiang, Tao[4];Cai, Zhuyun[1];Han, Junjie[1];Zhang, Haoyu[3];Xu, Bangzhe[1];Zhou, Xuhui[1];Wang, Ce[1]

机构：[1]Naval Med Univ, Changzheng Hosp, Dept Orthoped, Shanghai 200003, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China;[3]Second Mil Med Univ, Naval Med Univ, Inst Immunol, Natl Key Lab Med Immunol, Shanghai 200433, Peoples R China;[4]Changzhou Hosp Tradit Chinese Med, Changzhou 213000, Peoples R China

年份：2024

卷号：20

期号：33

外文期刊名：SMALL

收录：;EI(收录号：20241715990196);WOS:【SCI-EXPANDED(收录号:WOS:001207797900001)】；

基金：The authors are grateful to the Centre for Translational Medicine, Naval Military Medical University, China, for providing a harmonious working environment. The authors thank Professor Gu Yan of the National Key Immunology Centre of the Chinese Naval Military Medical University, Dr Liu Wei, Department of Spine Surgery, Changzheng Hospital, China Naval Medical University, China. Funding: This study was funded by the Shanghai Shuguang Programme (20SG37), Pyramid of Talent Project (1006).

语种：英文

外文关键词：adaptive immunoinflammation; bone repair; dendritic cell; magnesium ion; osteoimmunology

摘要：The effect of immunoinflammation on bone repair during the recovery process of bone defects needs to be further explored. It is reported that Mg2+ can promote bone repair with immunoregulatory effect, but the underlying mechanism on adaptive immunity is still unclear. Here, by using chitosan and hyaluronic acid-coated Mg2+ (CSHA-Mg) in bone-deficient mice, it is shown that Mg2+ can inhibit the activation of CD4+ T cells and increase regulatory T cell formation by inducing immunosuppressive dendritic cells (imDCs). Mechanistically, Mg2+ initiates the activation of the MAPK signaling pathway through TRPM7 channels on DCs. This process subsequently induces the downstream HIF-1 alpha expression, a transcription factor that amplifies TGF-beta production and inhibits the effective T cell function. In vivo, knock-out of HIF-1 alpha in DCs or using a HIF-1 alpha inhibitor PX-478 reverses inhibition of bone inflammation and repair promotion upon Mg2+-treatment. Moreover, roxadustat, which stabilizes HIF-1 alpha protein expression, can significantly promote immunosuppression and bone repair in synergism with CSHA-Mg. Thus, the findings identify a key mechanism for DCs and its HIF-1 alpha-TGF-beta axis in the induction of immunosuppressive bone microenvironment, providing potential targets for bone regeneration. Mg2+ promotes bone regeneration by inducing imDC suppression of effector T cell-mediated adaptive immune inflammation. Specifically, Mg2+ activates the MAPK signaling pathway through the TRPM7 channel on the DC surface, which in turn activates the HIF-1 alpha-TGF-beta axis to inhibit effector T cell activation. Induction of key target HIF-1 alpha expression by roxadustat significantly promotes regeneration in bone-deficient mice. image