N2-Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle.
N2-Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle.
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N2 极化中性粒细胞引导骨间充质干细胞募集并启动骨再生：骨再生难题中缺失的一块
DOI：
10.1002/advs.202100584
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Shen SGF
中科院分区：
文献类型：
--
作者：
Cai B;Lin D;Li Y;Wang L;Xie J;Dai T;Liu F;Tang M;Tian L;Yuan Y;Kong L;Shen SGF
中性粒细胞在骨再生中的作用仍然难以捉摸。本研究表明，肌肉内植入不同水平的白细胞介素-8 (IL-8)（通常被认为是中性粒细胞的趋化细胞因子）会导致与不同阶段的骨折血肿相似的结果。异位软骨内骨化是由一定水平的 IL-8 诱导的，在此过程中，中性粒细胞被募集到植入部位并进行 N2 极化，然后分泌基质细胞衍生因子 1α (SDF-1α)，通过 SDF-1/CXCR4（C-X-C 基序趋化因子受体 4）轴及其下游磷脂酰肌醇，促进骨间充质干细胞 (BMSC) 趋化3'-激酶 (PI3K)/Akt 途径和 β-连环蛋白介导的迁移。中性粒细胞对于招募和协调先天性和适应性免疫细胞以及骨愈合和再生初始阶段的骨髓间充质干细胞至关重要。本研究的结果描述了中性粒细胞启动的骨再生机制以及中性粒细胞和 BMSC 之间的相互作用以及先天性和适应性免疫。这项工作为骨再生治疗和生物材料开发领域的研究奠定了基础，并可能激发对新治疗方案的进一步研究。在骨缺损部位受到炎症刺激后，中性粒细胞首先到达，招募并协调先天性和适应性免疫细胞以及骨髓间充质干细胞，以在适当的免疫环境下启动软骨内骨化。在此过程中，N2极化中性粒细胞介导巨噬细胞和CD4+T细胞的抗炎转化，通过SDF-1/CXCR4轴及其下游PI3K/AKT通路和β-catenin介导的迁移分泌SDF-1α用于BMSC趋化。
The role of neutrophils in bone regeneration remains elusive. In this study, it is shown that intramuscular implantation of interleukin‐8 (IL‐8) (commonly recognized as a chemotactic cytokine for neutrophils) at different levels lead to outcomes resembling those of fracture hematoma at various stages. Ectopic endochondral ossification is induced by certain levels of IL‐8, during which neutrophils are recruited to the implanted site and are N2‐polarized, which then secrete stromal cell‐derived factor‐1α (SDF‐1α) for bone mesenchymal stem cell (BMSC) chemotaxis via the SDF‐1/CXCR4 (C‐X‐C motif chemokine receptor 4) axis and its downstream phosphatidylinositol 3'‐kinase (PI3K)/Akt pathway and β‐catenin‐mediated migration. Neutrophils are pivotal for recruiting and orchestrating innate and adaptive immunocytes, as well as BMSCs at the initial stage of bone healing and regeneration. The results in this study delineate the mechanism of neutrophil‐initiated bone regeneration and interaction between neutrophils and BMSCs, and innate and adaptive immunities. This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options. Following inflammatory stimuli at the bone defect site, neutrophils arrive first, recruit and orchestrate innate and adaptive immunocytes and BMSCs to initiate endochondral ossification under the appropriate immune environment. In this process, N2‐polarized neutrophils mediate anti‐inflammatory transformation of macrophages and CD4+ T cells, secrete SDF‐1α for BMSC chemotaxis via the SDF‐1/CXCR4 axis and its downstream PI3K/AKT pathway and β‐catenin‐mediated migration.
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DOI：
10.1073/pnas.102657399
发表时间：
2002-05-14
影响因子：
11.1
作者：
Cheon, SS;Cheah, AYL;Alman, BA
通讯作者：
Alman, BA
影响因子：
64.8
作者：
Deng, HK;Liu, R;Landau, NR
通讯作者：
Landau, NR
影响因子：
168.9
作者：
Askari, AT;Unzek, S;Penn, MS
通讯作者：
Penn, MS
影响因子：
56.9
作者：
HUBER, AR;KUNKEL, SL;WEISS, SJ
通讯作者：
WEISS, SJ
DOI：
10.1038/nrendo.2014.234
发表时间：
2015-03
期刊：
Nature reviews. Endocrinology
影响因子：
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作者：
通讯作者：
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