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| Title: | 在僵直性脊椎炎中，循環微型核糖核酸 (miR-27, miR-29, miR-125b, miR-146a, miR-155) 與其標的基因、發炎體基因多形性、骨重塑與發炎標記、以及臨床表徵之相關
Correlation between Circulating microRNAs (miR-27, miR-29, miR-125b, miR-146a, miR-155) and Their Target Genes, Inflammasome Genetic Polymorphism, Markers of Bone Remodelling and Inflammation, and Clinical Manifestations in Ankylosing Spondylitis |
| Authors: | 翁瑞宏 |
| Contributors: | 公共衛生學系 |
| Keywords: | 臨床醫學;公共衛生學 |
| Date: | 2014 |
| Issue Date: | 2015-02-25T09:17:26Z (UTC)
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| Abstract: | 僵直性脊椎炎 (ankylosing spondylitis；AS) 是項慢性風濕疾病，經常導致骨 骼變形。其致病機轉仍不清楚，重要的是具有兩個增強但是相對的骨重塑形態在 AS 中發生，一是病理性新骨形成，另一是骨質過度流失。微型核糖核酸 (microRNA; miR)-27 可抑制 sFRP1、DKK2 與 APC，miR-29也可抑制 sFRP2 與 DKK1 以調節 Wingless (Wnt) 訊息；當 Wnt 被活化，將誘發骨形成蛋白 (bone morphogenetic proteins；BMPs) 表現。TNF-α可能引發發炎與骨變化，miR-125b 可抑制 TNF-α表現，並且 miR-155 藉由鍵結 SOCS-1 以負向誘導 TNF-α表現。 另一方面，miR-21 鍵結至 PDCD4 也可誘發蝕骨細胞的活化。MiR-146a 也被提 議與 TRAF-6和 IRAK1 鍵結以抑制 NF-κB活性，然後增加標的基因包括 TNF-α 與 IL-1β 的轉譯。此外，IL-1β 在關節炎的骨質再吸收與軟骨破壞上具有效應， 發炎體 (inflammasome) 基因多形性也可能影響著 IL-1β 表現。我們設計一項病 例對照研究來比較在 AS 病患與健康對照之間 miR-27、miR-29、miR-125b、 miR-155、miR-21、miR-146a以及其標的基因表現的差異，並且評估在 AS 病患 中上述 miRNAs 與其標的基因表現、骨重塑與發炎標記、以及臨床表徵之相關。 非類固醇抗發炎藥物 (non-steroidal anti-inflammatory drugs; NSAIDs) 與疾病調 節抗風濕藥物 (disease modifying anti-rheumatic drugs; DMARDs) 在 AS 病患之 miRNAs 與其標的基因表現的影響也將被評估，miR-146a、IRAK1 以及發炎體基 因多形性在 AS 發生及相關分子表現程度的效應將被檢查，接受者操作特徵 (receiver operating characteristic) 曲線分析將被執行來決定所測試的miRNA表現 在診斷上來區隔 AS 病患與健康對照的效能。
Ankylosing spondylitis (AS) is a chronic rheumatic disorder that usually causes bone deformation. The definite pathogenesis of AS is still unknown. Importantly, there are two enhanced but opposite types of bone remodeling taking place in AS. One is pathologic new bone formation; another is excessive loss of bone mass. MicroRNA (miR)-27 might suppress sFRP1, DKK2 and APC, and miR-29 might suppress sFRP2 and DKK1 to regulate the Wingless (Wnt) signals. When Wnt is activated, it would induce the bone morphogenetic proteins (BMPs) expressions. TNF-α might induce the inflammation and bone turnover. MiR-125b might inhibit the TNF-α expression, and miR-155 inversely induces TNF-α expression by targeting SOCS-1. On the other hand, the binding of miR-21 to PDCD4 could also induce the activation of osteoclasts. It was also proposed miR-146a targeted TRAF-6 and IRAK1 to suppress NF-κB activity, which subsequently increases the transcription of target genes including TNF-α and IL-1β. In addition, IL-1β has an effect on the bone resorption of arthritis and cartilage damage. Inflammasome genetic polymorphisms might also affect the IL-1β expression. We design a case-control study to compare the expression differences of miR-27, miR-29, miR-125b, miR-155, miR-21, miR-146a, and their target genes between AS patients and healthy controls; and evaluate the relationships of the above miRNAs and their target gene expressions, markers of bone remodelling and inflammation, and clinical manifestations in AS patients. The influences of nonsteroidal antiinflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs) on the expressions of miRNAs and their target genes in AS patients will also be assessed. The effect of miR-146a, IRAK1, and inflammasome genetic polymorphisms on AS occurrence and related molecular expression levels will be examined. Receiver operating characteristic analysis will be performed to determine the diagnostic performance of the tested miRNA expressions in distinguishing AS patients from the healthy control subjects. |
| URI: | https://ir.csmu.edu.tw:8080/ir/handle/310902500/10299 |
| Appears in Collections: | [公共衛生學系暨碩士班] 研究計劃
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