Regulatory mechanisms of circular RNAs during human mesenchymal stem cell osteogenic differentiation

Abstract

Human osteogenic differentiation is a complex and well-orchestrated process which involves a plethora of molecular players and cellular processes. A growing number of studies have underlined that circular RNAs (circRNAs) play an important regulatory role during human osteogenic differentiation. CircRNAs are single-stranded, covalently closed non-coding RNA molecules that are acquiring increased attention as epigenetic regulators of gene expression. Given their intrinsic high conformational stability, abundance, and specificity, circRNAs can undertake various biological activities in order to regulate multiple cellular processes, including osteogenic differentiation. The most recent evidence indicates that circRNAs control human osteogenesis by preventing the inhibitory activity of miRNAs on their downstream target genes, using a competitive endogenous RNA mechanism. The aim of this review is to draw attention to the currently known regulatory mechanisms of circRNAs during human osteogenic differentiation. Specifically, we provide an understanding of recent advances in research conducted on various human mesenchymal stem cell types that underlined the importance of circRNAs in regulating osteogenesis. A comprehensive understanding of the underlying regulatory mechanisms of circRNA in osteogenesis will improve knowledge on the molecular processes of bone growth, resulting in the potential development of novel preclinical and clinical studies and the discovery of novel diagnostic and therapeutic tools for bone disorders.

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“…CircRNAs contain a high concentration of miRNA response elements and can competitively bind to miRNAs to form a ceRNA regulatory network. 26 MiRNAs are a type of non-coding RNA that are approximately 22 nt in length. They play a crucial role in post-transcriptional regulation by binding to specific sites in the 3′ untranslated region of mRNA.…”

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“…3 Osteoporosis is a chronic disease that is often overlooked and neglected. 4,5 Patients frequently discover they have osteoporosis only after experiencing a fracture, which can lead to substantial financial losses. T2DM has been found to be one of the highest risks for the occurrence of fractures.…”

Assessment of Reference Genes Stability in Cortical Bone of Obese and Diabetic Mice

“…4,5 The expression of non-coding RNAs, including small, long, and circular types, is also involved in bone development and the pathogenesis of bone-related disorders. [6][7][8] Circular RNAs affect bone formation by regulating specific gene expression. 6 MicroRNAs (like miR-30, miR-124, miR-204) and long non-coding RNAs also play significant roles in bone growth and stability.…”

“…[6][7][8] Circular RNAs affect bone formation by regulating specific gene expression. 6 MicroRNAs (like miR-30, miR-124, miR-204) and long non-coding RNAs also play significant roles in bone growth and stability. 7,8 Dysregulations that disrupt this genetic equilibrium within the skeletal framework can engender a spectrum of skeletal disorders, encompassing conditions such as osteoporosis, osteoarthritis, and osteogenic neoplasms.…”