Abstract

Osteoporosis is a major concern worldwide and can be attributed to an imbalance between osteoblastic bone formation and osteoclastic bone resorption due to the natural aging process. Heritable factors account for 60–80% of optimal bone mineralization; however, the finer details of pathogenesis remain to be elucidated. Micro RNA (miRNA) and long-non-coding RNA (lncRNA) are two targets that have recently come into the spotlight due to their ability to control gene expression at the post-transcriptional level and provide epigenetic modification. miRNAs are a class of non-coding RNAs that are approximately 18–25 nucleotides long. It is thought that up to 60% of human protein-coding genes may be regulated by miRNAs. They have been found to regulate gene expression that controls osteoblast-dependent bone formation and osteoclast-related bone remodeling. lncRNAs are highly structured RNA transcripts longer than 200 nucleotides that do not translate into proteins. They have very complex secondary and tertiary structures and the same degradation processes as messenger RNAs. The fact that they have a rapid turnover is due to their sponge function in binding the miRNAs that lead to a degradation of the lncRNA itself. They can act as signaling, decoy, and framework molecules, or as primers. Current evidence suggests that lncRNAs can act as chromatin and transcriptional as well as post-transcriptional regulators. With regards to osteoporosis, lncRNA is thought to be involved in the proliferation, apoptosis, and inflammatory response of the bone. This review, which is based on a systematic appraisal of the current literature, provides current molecular and genetic opinions on the roles of miRNAs and lncRNAs in osteoporosis. Further research into the epigenetic modification and the regulatory roles of these molecules will bring us closer to potential disease-modifying treatment for osteoporosis. However, more issues regarding the detailed actions of miRNAs and lncRNAs in osteoporosis remain unknown and controversial and warrant future investigation.

Highlights

  • Osteoporosis is increasing in prevalence around the world due to the aging population

  • Micro RNA and long-non-coding RNA are two such targets that have recently come into the spotlight due to their ability to control gene expression at the post-transcriptional level, providing epigenetic modification [2,3]. miRNAs are a class of non-coding RNAs that are approximately 18–25 nucleotides long [4]

  • We aim to summarize the current evidence on the actions of various miRNA and long-non-coding RNA (lncRNA)

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Summary

Introduction

Osteoporosis is increasing in prevalence around the world due to the aging population. It is thought that up to 60% of human protein-coding genes may be regulated by miRNAs [2,5] They bind to the 3-untranslated regions (3-UTR) of target genes, leading to messenger RNA (mRNA) degradation and transcription inhibition [2,6]. The process of miRNA regulation is complex, as each miRNA binds to a number of targets, and several miRNAs target the same mRNA [2] They have been found to regulate most biological processes, including cell development, differentiation, proliferation, metabolism, and cell cycle regulation [2]. They have been found to regulate gene expression that controls osteoblast-dependent bone formation and osteoclast-related bone remodeling [3,7]. In a study of 30 osteoporosis patients, miR-9-5p was found to be more highly expressed in the serum of osteoporosis patients compared to healthy controls [14]

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