Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation.
Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation.
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DOI：
10.1002/jor.23652
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Ahn J
中科院分区：
文献类型：
--
作者：
Hebb JH;Ashley JW;McDaniel L;Lopas LA;Tobias J;Hankenson KD;Ahn J
与年轻患者相比，老年骨折需要更长的愈合时间和更多的并发症；然而，这种愈合差异的机制基础还不是很清楚。为了更好地理解这一点，我们利用高通量的基因表达分析，研究了5个月大(青年)和25个月大(老年)小鼠骨折愈合过程中细胞和分子的差异。小鼠双侧胫骨骨折，分别于骨折后5、10、20天采集骨痂进行分析。用Affymetrix Mogene 1.0ST微阵列进行整体基因表达分析。归一化后，使用方差分析比较数据，并使用主成分分析(PCA)、CTEN、热图和Incromap分析进行评估。主成分分析和横截面热图分析表明，DPF和AGE对基因表达的变化有明显的影响。未骨折和20DPF的老龄小鼠均表现出免疫相关基因(CXCL8、CCL8和CCL5)的表达增加，而在10DPF时，老龄小鼠的基质相关基因(Matn1、Ucma、Scube1、Col9a1和Col9a3)的表达增加。CTEN分析表明，相对于年轻成年小鼠，老年小鼠的CD8+细胞和巨噬细胞丰富，相反，年轻成年小鼠相对于老年小鼠肥大细胞的比例更高。最后，与PCA数据一致，BMP、印度刺猬、Notch和Wnt的经典骨愈合途径按骨折后第一时间和第二年龄聚为一类。
Geriatric fractures take longer to heal and heal with more complications than those of younger patients; however, the mechanistic basis for this difference in healing is not well understood. To improve this understanding, we investigated cell and molecular differences in fracture healing between 5 month-old (young adult) and 25 month-old (geriatric) mice healing utilizing high-throughput analysis of gene expression. Mice underwent bilateral tibial fractures and fracture calluses were harvested at 5, 10, and 20 days post fracture (DPF) for analysis. Global gene expression analysis was performed using Affymetrix MoGene 1.0 ST microarrays. After normalization, data were compared using ANOVA and evaluated using Principal Component Analysis (PCA), CTen, heatmap, and Incromaps analysis. PCA and cross-sectional heatmap analysis demonstrated that DPF followed by age had pronounced effects on changes in gene expression. Both un-fractured and 20 DPF aged mice showed increased expression of immune associated genes (CXCL8, CCL8, and CCL5) and at 10 DPF, aged mice showed increased expression of matrix-associated genes, (Matn1, Ucma, Scube1, Col9a1, and Col9a3). Cten analysis suggested an enrichment of CD8+ cells and macrophages in old mice relative to young adult mice and, conversely, a greater prevalence of mast cells in young adult mice relative to old. Finally, consistent with the PCA data, the classic bone healing pathways of BMP, Indian Hedgehog, Notch and Wnt clustered according to the time post-fracture first and age second.
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