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微小RNA:慢性肾脏病中骨脆性的新兴生物标志物和治疗靶点

MicroRNAs: emerging biomarkers and therapeutic targets of bone fragility in chronic kidney disease.

作者信息

Smout Dieter, Van Craenenbroeck Amaryllis H, Jørgensen Hanne Skou, Evenepoel Pieter

机构信息

Department of Microbiology, Immunology and Transplantation; Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium.

Department of Medicine, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium.

出版信息

Clin Kidney J. 2022 Oct 7;16(3):408-421. doi: 10.1093/ckj/sfac219. eCollection 2023 Mar.

Abstract

Bone fragility is highly prevalent, yet underdiagnosed in patients with chronic kidney disease. Incomplete understanding of the pathophysiology and limitations of current diagnostics contribute to therapeutic hesitation, if not nihilism. This narrative review addresses the question of whether microRNAs (miRNAs) may improve therapeutic decision making in osteoporosis and renal osteodystrophy. miRNAs are key epigenetic regulators of bone homeostasis and show promise as both therapeutic targets and as biomarkers, primarily of bone turnover. Experimental studies show that miRNAs are involved in several osteogenic pathways. Clinical studies exploring the usefulness of circulating miRNAs for fracture risk stratification and for guiding and monitoring therapy are few and, so far, provide inconclusive results. Likely, (pre)analytical heterogeneity contributes to these equivocal results. In conclusion, miRNAs are promising in metabolic bone disease, both as a diagnostic tool and as therapeutic targets, but not yet ready for clinical prime time.

摘要

骨脆性非常普遍,但在慢性肾病患者中却未得到充分诊断。对病理生理学的不完全理解以及当前诊断方法的局限性导致了治疗上的犹豫,甚至是虚无主义。这篇叙述性综述探讨了微小RNA(miRNA)是否可以改善骨质疏松症和肾性骨营养不良的治疗决策。miRNA是骨稳态的关键表观遗传调节因子,作为治疗靶点和生物标志物(主要是骨转换的生物标志物)都具有前景。实验研究表明,miRNA参与了多种成骨途径。探索循环miRNA在骨折风险分层以及指导和监测治疗方面有用性的临床研究很少,而且到目前为止,结果尚无定论。很可能,(前)分析异质性导致了这些模棱两可的结果。总之,miRNA在代谢性骨病中作为诊断工具和治疗靶点都很有前景,但尚未准备好进入临床应用阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a62/9972833/4a3a3d6ff439/sfac219fig1.jpg

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