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微小 RNA 在强直性脊柱炎发病机制中的作用及其临床意义。

MicroRNAs in the Pathogenesis of Ankylosing Spondylitis and their Clinical Implication.

机构信息

Department of Orthopedics, Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430063, China.

Department of Pediatric General Internal Medicine, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, Gansu 730050, China.

出版信息

Curr Mol Med. 2023;23(10):1058-1065. doi: 10.2174/1566524023666221103155119.

Abstract

Ankylosing spondylitis (AS) is a chronic and progressive immunoinflammatory disease, which mainly affects the spine and sacroiliac joints and shows a high rate of late disability. Inflammation, bone destruction, and new bone formation are typical pathological changes of AS. AS is dominated by inflammation at the early stage. While bone destruction and heterotopic ossification, the two contradictory manifestations of AS, occur at a later stage and reflect the imbalance between osteogenesis and osteoclastogenesis in AS patients. Till now, the pathogenesis of AS remains unclear. MicroRNAs (miRNAs) are a class of highly conserved single-stranded noncoding RNAs (ncRNAs) with a length of about 22 bases characterized by temporal sequence and tissue specificity. MiRNAs are key modulators in bone formation, resorption, remodeling and regeneration by regulating the immune responses and the differentiation and functions of osteoblasts, osteoclasts and chondrocytes. The present review summarizes the roles and potential mechanisms of miRNAs' involvement in AS by regulating immuno-inflammatory responses, bone destruction, heterotopic ossification, cell death and autophagy, and the involved signaling including the Wnt/β-catenin and BMP/Smads pathways. In addition, the feasibility of miRNAs as diagnostic biomarkers and therapeutic targets for AS are also discussed.

摘要

强直性脊柱炎(AS)是一种慢性、进行性的免疫炎症性疾病,主要累及脊柱和骶髂关节,晚期致残率高。炎症、骨破坏和新骨形成是 AS 的典型病理改变。AS 以早期炎症为主,而骨破坏和异位骨化是 AS 的两个矛盾表现,发生在后期,反映了 AS 患者成骨和破骨之间的失衡。目前,AS 的发病机制尚不清楚。微小 RNA(miRNA)是一类高度保守的单链非编码 RNA(ncRNA),长度约为 22 个碱基,具有时间序列和组织特异性。miRNA 通过调节免疫反应以及成骨细胞、破骨细胞和软骨细胞的分化和功能,是骨形成、吸收、重塑和再生的关键调节因子。本文综述了 miRNA 通过调节免疫炎症反应、骨破坏、异位骨化、细胞死亡和自噬,以及涉及的信号通路(包括 Wnt/β-catenin 和 BMP/Smads 通路)在 AS 中的作用及其潜在机制。此外,还讨论了 miRNA 作为 AS 诊断生物标志物和治疗靶点的可行性。

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