AUTHOR=Kharaz Yalda A. , Zamboulis Danae E. , Fang Yongxiang , Welting Tim J. M. , Peffers Mandy J. , Comerford Eithne J. 

TITLE=Small RNA signatures of the anterior cruciate ligament from patients with knee joint osteoarthritis

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1266088

DOI=10.3389/fmolb.2023.1266088

ISSN=2296-889X

ABSTRACT=The anterior cruciate ligament (ACL) is susceptible to degeneration, resulting in joint pain, reduced mobility and osteoarthritis development. There is currently a paucity of knowledge on how anterior cruciate ligament degeneration and disease leads to osteoarthritis. Small non-coding RNAs (sncRNAs), such as microRNAs, and small nucleolar RNA, have diverse roles including regulation of gene expression. We profiled the sncRNAs of diseased osteoarthritic ACLs to provide novel insights into osteoarthritis development. Small RNA sequencing from the ACLs of non- or end-stage human osteoarthritic knee joints was performed. Significantly differentially expressed sncRNAs were defined and bioinformatic analysis was undertaken. A total of 184 sncRNAs were differentially expressed; 68 small nucleolar RNAs, 26 small nuclear RNAs and 90 microRNAs. We identified both novel and recognised (miR-206, -365 and -29b and -29c) osteoarthritis-related microRNAs and other sncRNAs (including SNORD72, SNORD113, SNORD114). Significant pathway enrichment of differentially expressed miRNAs, including differentiation of muscle, inflammation, proliferation of chondrocytes and fibrosis. Putative mRNAs of the microRNA target genes were associated with the canonical pathways ‘Hepatic Fibrosis Signalling’, and ‘Osteoarthritis’. The establishing sncRNA signatures of ACL disease during osteoarthritis could serve as novel biomarkers and potential therapeutic targets in ACL degeneration and osteoarthritis development.