Changes in Transcriptome-Wide Gene Expression of Anterior Cruciate Ligament Tears Based on Time From Injury
Changes in Transcriptome-Wide Gene Expression of Anterior Cruciate Ligament Tears Based on Time From Injury
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DOI：
10.1177/0363546516643810
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发表时间：
2016-08-01
影响因子：
4.8
通讯作者：
Rai, Muhammad Farooq
中科院分区：
文献类型：
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作者：
Brophy, Robert H.;Tycksen, Eric D.;Rai, Muhammad Farooq
背景：前交叉韧带（ACL）撕裂是一种常见的损伤。受伤ACL的愈合潜力知之甚少，被认为是有限的。因此，大多数手术治疗的ACL撕裂进行重建，而不是修复。然而，最近有新的兴趣在修复ACL撕裂，尽管未回答的问题，愈合能力的ACL.Hypothesis：基因表达在受伤的ACL随着时间的变化从injure.Study Design：描述性laboratory study.Methods：转录组范围内的表达谱的24人ACL残余物在手术重建时恢复进行了分析，使用安捷伦人类8x 60 K微阵列平台。基于损伤时间（急性，12个月）对差异表达的转录物进行基因本体论。通过微流控数字聚合酶链反应验证任何2类之间的表达与大的倍数变化的转录本的子集。结果：许多转录本代表重要的生物过程的差异表达的时间从损伤。急性组和慢性组之间的变化最为显著。与急性和中度泪液相比，慢性泪液中的几种细胞外基质基因，即POR 4、COL 5A 1、COL 1A 1和COL 12 A1的表达较低。在急性泪液中，代表血管生成和干细胞分化的过程受到影响。在中间的眼泪，代表干细胞增殖伴随着细胞成分组织/细胞定位的过程被改变。在ACL撕裂超过12个月的损伤，过程表示肌球蛋白丝组织，细胞成分组织/细胞定位，和细胞外基质组织受到影响。结论：这些研究结果是一致的初始修复活动在受伤的ACL，随着时间的推移从损伤。在这项研究中确定的个别基因，如骨膜蛋白，值得进一步调查他们的作用，在组织repair.Clinical Relevance：随着时间的推移，ACL撕裂的愈合能力下降是相关的发展，有效的技术，用于修复ACL撕裂，并可能有一定的意义ACL重建技术，以及。急性ACL撕裂的愈合潜力似乎最大，这表明该窗口应该是ACL修复研究的重点。
Background: Anterior cruciate ligament (ACL) tears are a common injury. The healing potential of the injured ACL is poorly understood and is considered limited. Therefore, most ACL tears that are treated surgically undergo reconstruction rather than repair. However, there has been renewed interest recently in repairing ACL tears despite unanswered questions regarding the healing capacity of the ACL.Hypothesis: Gene expression in the injured ACL varies with time from injury.Study Design: Descriptive laboratory study.Methods: Transcriptome-wide expression profiles of 24 human ACL remnants recovered at the time of surgical reconstruction were analyzed using the Agilent human 8x60K microarray platform. Gene ontology was performed on differentially expressed transcripts based on time from injury (acute, 12 months). A subset of transcripts with large fold changes in expression between any 2 categories was validated via microfluidic digital polymerase chain reaction.Results: Numerous transcripts representing important biological processes were differentially expressed by time from injury. The most significant changes were noted between the acute and chronic groups. Expression of several extracellular matrix genes namely, POSTN, COL5A1, COL1A1, and COL12A1was lower in the chronic tears compared with acute and intermediate tears. In acute tears, processes representing angiogenesis and stem cell differentiation were affected. In intermediate tears, processes representing stem cell proliferation concomitant with cellular component organization/cellular localization were altered. In ACL tears more than 12 months out from injury, processes denoting myosin filament organization, cellular component organization/cell localization, and extracellular matrix organization were affected.Conclusion: These findings are consistent with initial repair activity in the injured ACL, which declines with time from injury. Individual genes identified in this study, such as periostin, deserve further investigation into their role in tissue repair.Clinical Relevance: The decreased healing capacity of ACL tears over time is relevant to the development of effective techniques for repairing ACL tears and may have some significance for ACL reconstruction techniques as well. The potential for healing appears to be greatest in acute ACL tears, suggesting this window should be the focus of research for ACL repair.