Magnetic responsive hydroxyapatite scaffold modulated macrophage polarization through PPAR/JAK-STAT signaling and enhanced fatty acid metabolism.
Magnetic responsive hydroxyapatite scaffold modulated macrophage polarization through PPAR/JAK-STAT signaling and enhanced fatty acid metabolism.
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DOI：
10.1016/j.biomaterials.2023.122051
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发表时间：
2023-02
期刊：
影响因子：
14
通讯作者：
Xiaoqing Sun;Yichun Gao;Zhiyu Li;Jing He;Yao Wu
中科院分区：
文献类型：
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作者：
Xiaoqing Sun;Yichun Gao;Zhiyu Li;Jing He;Yao Wu
尽管磁刺激对骨修复的作用已得到广泛的研究，但磁刺激在骨愈合过程中巨噬细胞反应中的作用机制尚未得到系统的研究。在此，通过将磁性纳米颗粒引入羟基磷灰石支架中，在骨愈合期间实现了从促炎（M1）到抗炎（M2）巨噬细胞的适当和及时的转变。结合蛋白质组学和基因组学的分析，从蛋白质冠和细胞内信号转导的角度揭示了磁线索介导的巨噬细胞极化的潜在机制。我们的研究结果表明，支架中固有的磁性线索有助于上调过氧化物酶体增殖物激活受体（PPAR）信号，激活巨噬细胞中的PPAR信号转导导致Janus激酶信号转导和转录激活因子（JAK-STAT）信号下调，脂肪酸代谢增强，从而促进巨噬细胞的M2极化。巨噬细胞中的磁线索依赖性变化受益于与“激素”和“对激素的反应”相关的吸附蛋白的上调，以及与蛋白质冠中的“酶联受体信号传导”相关的吸附蛋白的下调。此外，磁性支架还可以与外部磁场协同作用，进一步抑制M1型极化。本研究表明，磁信号在M2极化、偶联蛋白冠、细胞内PPAR信号和代谢中起着关键作用。
Despite the general observations of bone repair with magnetic cues, the mechanisms of magnetic cues in macrophage response during bone healing have not been systematically investigated. Herein, by introducing magnetic nanoparticles into hydroxyapatite scaffolds, an appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) macrophages during bone healing is achieved. The combined use of proteomics and genomics analysis reveals the underlying mechanism of magnetic cue-mediated macrophage polarization form the perspective of protein corona and intracellular signal transduction. Our results suggest that intrinsically-present magnetic cues in scaffold contribute to the upregulated peroxisome proliferator-activated receptor (PPAR) signals, and the activation of PPAR signal transduction in macrophages results in the downregulation of the Janus Kinase-Signal transducer and activator of transcription (JAK-STAT) signals and the enhancement of fatty acid metabolism, thus facilitating M2 polarization of macrophages. Magnetic cue-dependent changes in macrophage benefit from the upregulation of adsorbed proteins associated with “hormone” and “response to hormone”, as well as the downregulation of adsorbed proteins related to “enzyme-linked receptor signaling” in the protein corona. In addition, magnetic scaffolds may also act cooperatively with the exterior magnetic field, showing further inhibition of M1-type polarization. This study demonstrates that magnetic cues play critical roles on M2 polarization, coupling protein corona, intracellular PPAR signals and metabolism.