Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments.

Julian Zacharjasz,Paweł Bąkowski,Anna M Mleczko,Tomasz Piontek,Kamilla Bąkowska-Żywicka

doi:10.3390/ijms22115711

Abstract

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world’s population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.

Highlights

Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder, that affected303 million people globally in 2017 [1]
The JAK-STAT kinase pathway regulates the expression of many cytokines, including IL-6, which has an important role in the pathogenesis of multiple diseases, including osteoarthritis. 30 -tRNA-derived fragments (tRFs)-Cys-GCA was able to suppress Janus kinase 3 (JAK3) kinase, which resulted in decreased expression of IL-6, indicating a potential role of this tRF in the regulation of OA pathogenesis
The knowledge of tRNA-derived fragments in OA is still sparse. This is surprising taking into consideration that in multiple tissues and organisms, tRFs are as abundant as miRNAs

Summary

Introduction

Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder, that affected. 303 million people globally in 2017 [1]. Been reported that unique small ncRNA expression signatures are believed to terize specificspecific types oftypes cells,of but alsobut to be indicative of particular diseases [11]. Imporportant for diagnostic biomarker discovery and the development of therapeutic agents tant for diagnostic biomarker discovery and the development of therapeutic agents [12,13,14,15] TRNA-derived fragments human man tissues, both types of these small molecules are abundant, with expression tissues, both types of these small ncRNA molecules are abundant, with expression patterns patterns that depend on a person’s sex and population origin. Dicer enzyme into the tRF, into the tRF, which is uploaded onto the RISC to regulate gene expression. This review article aims to provide a comprehensive update on the evidence for two types of small ncRNA roles in OA: microRNAs and tRNA-derived fragments

Pathophysiology and Diagnosis of Knee Osteoarthritis

Biochemistry of Osteoarthritis

Transcriptomics of Knee Osteoarthritis

MicroRNAs in Knee OA

Findings

Conclusions and Perspectives