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Age-related changes to macrophages are detrimental to fracture healing in mice.
Aging Cell ( IF 7.8 ) Pub Date : 2020-02-25 , DOI: 10.1111/acel.13112
Daniel Clark 1, 2 , Sloane Brazina 1 , Frank Yang 1 , Diane Hu 1 , Christine L Hsieh 3 , Erene C Niemi 3 , Theodore Miclau 1 , Mary C Nakamura 3 , Ralph Marcucio 1
Affiliation  

The elderly population suffers from higher rates of complications during fracture healing that result in increased morbidity and mortality. Inflammatory dysregulation is associated with increased age and is a contributing factor to the myriad of age‐related diseases. Therefore, we investigated age‐related changes to an important cellular regulator of inflammation, the macrophage, and the impact on fracture healing outcomes. We demonstrated that old mice (24 months) have delayed fracture healing with significantly less bone and more cartilage compared to young mice (3 months). The quantity of infiltrating macrophages into the fracture callus was similar in old and young mice. However, RNA‐seq analysis demonstrated distinct differences in the transcriptomes of macrophages derived from the fracture callus of old and young mice, with an up‐regulation of M1/pro‐inflammatory genes in macrophages from old mice as well as dysregulation of other immune‐related genes. Preventing infiltration of the fracture site by macrophages in old mice improved healing outcomes, with significantly more bone in the calluses of treated mice compared to age‐matched controls. After preventing infiltration by macrophages, the macrophages remaining within the fracture callus were collected and examined via RNA‐seq analysis, and their transcriptome resembled macrophages from young calluses. Taken together, infiltrating macrophages from old mice demonstrate detrimental age‐related changes, and depleting infiltrating macrophages can improve fracture healing in old mice.

中文翻译:

与年龄相关的巨噬细胞变化不利于小鼠骨折愈合。

老年人口在骨折愈合过程中的并发症发生率更高,从而导致发病率和死亡率增加。炎症失调与年龄增长有关,并且是多种与年龄有关的疾病的成因。因此,我们研究了与年龄有关的重要炎症细胞调节因子,巨噬细胞及其对骨折愈合结果的影响的变化。我们证明,与年轻小鼠(3个月)相比,老年小鼠(24个月)延迟了骨折愈合,骨骼明显减少,软骨增多。在老年和幼年小鼠中,进入骨折call的巨噬细胞浸润量相似。但是,RNA-seq分析表明,在成年小鼠和年幼小鼠的骨折愈伤组织中,巨噬细胞的转录组存在明显差异,会导致老年小鼠巨噬细胞中M1 /促炎基因的上调以及其他免疫相关基因的失调。防止老年小鼠巨噬细胞侵入骨折部位可改善愈合效果,与年龄匹配的对照组相比,治疗小鼠的老茧中的骨骼明显更多。防止巨噬细胞浸润后,收集残留在骨折call中的巨噬细胞,并通过RNA-seq分析进行检查,其转录组类似于年轻愈伤组织的巨噬细胞。综上所述,老年小鼠浸润性巨噬细胞显示出与年龄相关的有害变化,而耗尽浸润性巨噬细胞可以改善老年小鼠的骨折愈合。防止老年小鼠巨噬细胞侵入骨折部位可改善愈合效果,与年龄匹配的对照组相比,治疗小鼠的老茧中的骨骼明显更多。防止巨噬细胞浸润后,收集残留在骨折call中的巨噬细胞,并通过RNA-seq分析进行检查,其转录组类似于年轻愈伤组织的巨噬细胞。综上所述,老年小鼠浸润性巨噬细胞显示出与年龄相关的有害变化,而耗尽浸润性巨噬细胞可改善老年小鼠的骨折愈合。防止老年小鼠巨噬细胞侵入骨折部位可改善愈合效果,与年龄匹配的对照组相比,治疗小鼠的老茧中的骨骼明显更多。防止巨噬细胞浸润后,收集残留在骨折call中的巨噬细胞,并通过RNA-seq分析进行检查,其转录组类似于年轻愈伤组织的巨噬细胞。综上所述,老年小鼠浸润性巨噬细胞显示出与年龄相关的有害变化,而耗尽浸润性巨噬细胞可改善老年小鼠的骨折愈合。收集残留在骨折call中的巨噬细胞,并通过RNA-seq分析进行检查,其转录组类似于年轻愈伤组织的巨噬细胞。综上所述,老年小鼠浸润性巨噬细胞显示出与年龄相关的有害变化,而耗尽浸润性巨噬细胞可改善老年小鼠的骨折愈合。收集残留在骨折call中的巨噬细胞,并通过RNA序列分析进行检查,其转录组类似于年轻愈伤组织的巨噬细胞。综上所述,老年小鼠浸润性巨噬细胞显示出与年龄相关的有害变化,而耗尽浸润性巨噬细胞可改善老年小鼠的骨折愈合。
更新日期:2020-02-25
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