The function of lncRNAs in the pathogenesis of osteoarthritis

Abstract

Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2021;10(2):122–133.

Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

“…Transforming growth factor-β (TGF-β) maintains functions of articular cartilage by transducing Smad2/3 signals, thereby promoting collagen (Col2a1) and fibronectin synthesis and inhibiting ECM degradation induced by overloading ( Madej et al, 2016 ). Mechanical loading also causes differential expression of miRNAs ( Kwak et al, 2020 ) and lncRNAs ( He et al, 2021 ), which regulate the activities of MMPs and the progress of OA development.…”

“…Long noncoding RNA (lncRNA), more than 200 nucleotides, usually cannot be translated into proteins due to lack of an open reading frame ( Andrey and Duboule, 2014 ). Many dysregulated lncRNAs have been involved in the pathological changes of OA, including ECM degradation ( He et al, 2021 ). LncRNA H19 has been demonstrated to ameliorate the mechanical force-induced cartilage degeneration in developmental dysplasia of the hip by mediating miR-485/Dusp5 axis, as indicated by increased expression of COL2A1 and aggrecan and decreased expression of MMP3 and ADAMTS5 in intermittent cyclic mechanical stress (ICMS)-induced chondrocytes ( Wang et al, 2020 ).…”

Recent Advances in Pharmacological Intervention of Osteoarthritis: A Biological Aspect

“…In particular, research and development of therapeutic targets for OA provide important clues ( Cong et al, 2017 ). However, studies also report that many ncRNAs are considered the critical elements in cancer development ( He et al, 2021a ). Sufficient preclinical safety inspections should be performed before clinical use ( Xie et al, 2020a ).…”

The role of AGEs in pathogenesis of cartilage destruction in osteoarthritis

“…Osteoarthritis (OA) is the most common chronic and progressive degenerative joint disease, mainly characterized by progressive joint destruction. 1,2 Currently, the World Health Organization lists OA, cardiovascular disease, and cancer as the three major diseases threatening human health, and the overall incidence of OA is increasing annually. 3 OA not only seriously affects the quality of life of patients, but also places a heavy burden on the social economy and medical care system.…”