Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing.
Aging Affects Bone Marrow Macrophage Polarization: Relevance to Bone Healing.
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衰老会影响骨髓巨噬细胞极化：与骨愈合有关。
DOI：
10.1007/s40883-016-0016-5
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发表时间：
2016-06
影响因子：
2.6
通讯作者：
Goodman SB
中科院分区：
文献类型：
--
作者：
Gibon E;Loi F;Córdova LA;Pajarinen J;Lin T;Lu L;Nabeshima A;Yao Z;Goodman SB
巨噬细胞是炎症级联反应的重要组成部分，通过启动和调节导致组织再生和骨愈合的过程。根据局部环境的不同，巨噬细胞可以极化为M1（促炎）或M2（抗炎）表型。为了研究衰老对巨噬细胞功能的影响，采用幼年（8周龄）和老年（72周龄）野生型雄性C57BL/6J小鼠的原代骨髓巨噬细胞（BMMs）进行骨髓巨噬细胞极化分析。采用荧光活化细胞分选（FACS）分析（CD11b、iNOS、CD206）、qRT-PCR分析（iNOS、TNF-α、CD206、Arginase 1）和ELISA分析（TNF-α、IL-1ra）比较青年和老年小鼠巨噬细胞M1和M2表型标记。一旦确认M1和M2巨噬细胞表型，结果显示干扰素γ (INF-γ)暴露后，衰老M1中TNF-α mRNA显著上调。在老年巨噬细胞中，精氨酸酶1和CD206 mRNA的表达在il - 4刺激下仍然上调，但上调幅度小于幼年巨噬细胞。在脂多糖（LPS）暴露后，与年轻m1相比，老年m1的TNF-α分泌也显著增加。然而，老龄小鼠IL-1ra分泌并未相应增加。结果表明，与年轻动物相比，骨髓源性巨噬细胞的衰老增加了氧化应激的静息水平，以及促炎标志物与抗炎标志物的比率。这些与年龄相关的巨噬细胞极化变化可以部分解释老年人对不良刺激的反应减弱和骨折愈合等过程的延迟。骨愈合是一个复杂的过程，涉及生物和机械因素。巨噬细胞是调节骨愈合过程的关键细胞，尤其是炎症初期。在这个生物级联事件中，巨噬细胞以不同的功能表型存在，包括未承诺（M0），促炎（M1）和抗炎（M2），这一过程称为巨噬细胞极化。清楚地了解衰老对巨噬细胞极化的影响对于调节老龄化人群中的骨折、非创伤性骨质流失和组织再生等不良事件至关重要。
Macrophages are an important component of the inflammatory cascade by initiating and modulating the processes leading to tissue regeneration and bone healing. Depending on the local environment, macrophages can be polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes. In order to assess the effects of aging on macrophage function, bone marrow macrophage polarization using primary bone marrow macrophages (BMMs) from young (8 weeks old) and aged (72 weeks old) wild-type male C57BL/6J mice was analyzed. Fluorescence-activated cell sorting (FACS) analysis (CD11b, iNOS, CD206), qRT-PCR (iNOS, TNF-α, CD206, Arginase 1), and ELISA (TNF-α, IL-1ra) were performed to compare the M1 and M2 phenotypic markers in young and aged mouse macrophages. Once M1 and M2 macrophage phenotypes were confirmed, the results showed that TNF-α mRNA was significantly upregulated in aged M1s after interferon gamma (INF-γ) exposure. Arginase 1 and CD206 mRNA expression were still upregulated with IL4 stimulation in aged macrophages, but to a lesser extend than those from younger animals. TNF-α secretion was also significantly increased in aged M1s compared to young M1s, following lipopolysaccharide (LPS) exposure. However, the IL-1ra secretion did not increase accordingly in aged mice. The results demonstrate that, compared to younger animals, aging of bone marrow derived macrophages increases the resting levels of oxidative stress, and the ratios of pro- to anti-inflammatory markers. These age-related changes in macrophage polarization may explain in part the attenuated response to adverse stimuli and delay in processes such as fracture healing seen in the elderly. Bone healing is a complex process that involves both biological and mechanical factors. Macrophages are key cells that regulate the events involved in bone healing, especially the initial inflammatory phase. In this biological cascade of events, macrophages present as different functional phenotypes including uncommitted (M0), pro-inflammatory (M1), and anti-inflammatory (M2), a process called macrophage polarization. A clear understanding of the effects of aging on macrophage polarization is critical to modulating adverse events such as fractures, atraumatic bone loss, and tissue regeneration in an aging population.