A Network Biology Approach to Understanding the Tissue-Specific Roles of Non-Coding RNAs in Arthritis

Abstract

Discovery of non-coding RNAs continues to provide new insights into some of the key molecular drivers of musculoskeletal diseases. Among these, microRNAs have received widespread attention for their roles in osteoarthritis and rheumatoid arthritis. With evidence to suggest that long non-coding RNAs and circular RNAs function as competing endogenous RNAs to sponge microRNAs, the net effect on gene expression in specific disease contexts can be elusive. Studies to date have focused on elucidating individual long non-coding-microRNA-gene target axes and circular RNA-microRNA-gene target axes, with a paucity of data integrating experimentally validated effects of non-coding RNAs. To address this gap, we curated recent studies reporting non-coding RNA axes in chondrocytes from human osteoarthritis and in fibroblast-like synoviocytes from human rheumatoid arthritis. Using an integrative computational biology approach, we then combined the findings into cell- and disease-specific networks for in-depth interpretation. We highlight some challenges to data integration, including non-existent naming conventions and out-of-date databases for non-coding RNAs, and some successes exemplified by the International Molecular Exchange Consortium for protein interactions. In this perspective article, we suggest that data integration is a useful in silico approach for creating non-coding RNA networks in arthritis and prioritizing interactions for further in vitro and in vivo experimentation in translational research.

Transcriptomics and metabolomics: Challenges of studying obesity in osteoarthritis

“…Therefore, single miRNA or metabolite level differences associated with obesity-related OA may be more difficult to identify, and targeting a single miRNA or metabolite may only produce partial therapeutic responses due to this redundancy. To overcome this challenge, the use computational and machine learning techniques to investigate networks of miRNA [ 70 ] and metabolite [ 71 ] signatures highly associated with obesity-related OA may be better to discover targets to monitor or treat obese OA patients.…”

Why Does Rehabilitation Not (Always) Work in Osteoarthritis? Does Rehabilitation Need Molecular Biology?

“…The computational biology when exploring biological data via artificial neural networks; deep-learning supports efficiently molecular biology [109][110][111]. Some molecular relations cannot be revealed without use of computational techniques [112].…”

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

“…Novel functions reported for snoRNAs include modulation of alternative splicing (Khanna and Stamm, 2010), involvement in stress response pathways (Michel et al, 2011), and modulation of mRNA 3′ end processing (Huang et al, 2017). Like miRNAs, snoRNAs are emerging as important regulators of cellular function and OA development (Peffers et al, 2020;Ripmeester et al, 2020;Ali et al, 2021a;Ali et al, 2021b), in part due to their ability to fine-tune the ribosome to accommodate changing requirements for protein production during development, normal function, and disease (Montanaro et al, 2008;van den Akker et al, 2022).…”