Human Early Fracture Hematoma Is Characterized by Inflammation and Hypoxia
Human Early Fracture Hematoma Is Characterized by Inflammation and Hypoxia
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DOI：
10.1007/s11999-011-1865-3
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发表时间：
2011-11-01
影响因子：
4.2
通讯作者：
Buttgereit, Frank
中科院分区：
文献类型：
--
作者：
Kolar, Paula;Gaber, Timo;Buttgereit, Frank
一个有效的免疫系统，特别是在炎症阶段，脓毒症影响骨愈合的质量和可能性。这是否以及如何反映在最初的骨折血肿中尚不清楚，因此我们提出了以下问题：（1）与外周血相比，骨折血肿中与缺氧适应、迁移、血管生成和骨生成相关的基因的局部表达是否不同？(2)这些变化是否与时间有关？(3)骨折血肿形成过程中的基因表达是否因辐射而改变？20例患者骨折血肿中的细胞和40例患者全髋关节置换术后血肿形成分离并提取RNA，分析骨折愈合过程中缺氧对基因mRNA表达的影响。（HIF 1A、LDHA和PGK 1）参与免疫调节（IL 6、IL 8、CXCR 4）、血管生成（VEGF，IL 8）和骨生成（SPP1，我们观察到骨折血肿细胞局部LDHA基因表达增加，（骨折后6-72 h）反映了对缺氧的适应。IL 6、IL 8和VEGF上调表明缺氧介导的炎症和血管生成; CXCR 4表达增加反映了免疫细胞的迁移。成骨分化反映在SPP 1和RUNX 2基因的表达增加。LDHA、VEGF、IL 8、SPP 1和RUNX 2基因表达的增加呈时间依赖性。辐射抑制HIF 1A、IL 6、IL 8、CXCR 4和RUNX 2基因表达。我们的数据表明骨折血肿中的细胞（1）适应缺氧，（2）在mRNA水平上促进骨折愈合中的炎症反应，表明免疫系统的早期参与。最初的骨折血肿对血管生成、趋化性和骨生成的发生很重要。
An effective immune system, especially during the inflammatory phase, putatively influences the quality and likelihood of bone healing. If and how this is reflected within the initial fracture hematoma is unclear.We therefore asked the following questions: (1) Does the local expression in fracture hematoma of genes involved in adaptation to hypoxia, migration, angiogenesis, and osteogenesis vary as compared to the peripheral blood? (2) Do these changes occur time dependently? (3) Is the gene expression during fracture hematoma formation altered by irradiation?Cells from fracture hematoma of 20 patients and hematomas formed in 40 patients after THA (20 without and 20 with preoperative radiation) were isolated and RNA was extracted to analyze the influence of oxygen deprivation during fracture healing on mRNA expression of genes (HIF1A, LDHA, and PGK1) involved in immunoregulation (IL6, IL8, CXCR4), angiogenesis (VEGF, IL8), and osteogenesis (SPP1, RUNX2) by quantitative PCR.We observed locally increased LDHA gene expression in fracture hematoma cells (6-72 h post fracture) reflecting the adaptation to hypoxia. IL6, IL8, and VEGF upregulation indicated hypoxia-mediated inflammation and angiogenesis; increased CXCR4 expression reflected immigration of immune cells. Osteogenic differentiation was reflected in the increased expression of the SPP1 and RUNX2 genes. The increased expression of the LDHA, VEGF, IL8, SPP1 and RUNX2 genes occurred time dependently. Irradiation suppressed HIF1A, IL6, IL8, CXCR4, and RUNX2 gene expression.Our data suggest cells in the fracture hematoma (1) adapt to hypoxia and (2) promote inflammation in fracture healing at the mRNA level, indicating early involvement of the immune system.The initial fracture hematoma is important for the onset of angiogenesis, chemotaxis, and osteogenesis.