Noncoding RNA miR‐205‐5p mediates osteoporosis pathogenesis and osteoblast differentiation by regulating RUNX2

Abstract

As a kind of noncoding RNAs, microRNAs (miRNAs) play important roles in disease pathogenesis by regulating gene expression. However, the molecular mechanism of miRNAs in osteoporosis remains largely unknown. In the present study, we aim to explore the genome‐wide miRNAs expression profile and the regulatory mechanism of miR‐205‐5p in osteoporosis. A total of 72 differentially expressed miRNAs were identified in osteoporosis via microarray technology and bioinformatics analysis. We focused on one of the abnormally expressed miRNAs, miR‐205‐5p, which was previously unknown in osteoporosis. Quantitative real‐time polymerase chain reaction (qRT‐PCR) results showed that miR‐205‐5p was upregulated in osteoporosis samples and its expression was gradually decreased during osteogenic differentiation. Besides, miR‐205‐5p overexpression could inhibit the activity of osteoblast markers, including collagen, type I, α 1 (COL1A1) and alkaline phosphatase (ALP) while miR‐205‐5p inhibition showed the opposite results. Moreover, bioinformatics analysis identified the potential targets of miR‐205‐5p, including runt‐related transcription factor 2 (RUNX2), SMAD1 and BCL6, etc. The dual‐luciferase reporter assay confirmed RUNX2 was directly targeted by miR‐205‐5p. Furthermore, the rescue experiments showed that RUNX2 overexpression could significantly weaken the effect of miR‐205‐5p on osteoblast markers, indicating that miR‐205‐5p may inhibit osteogenic differentiation by targeting RUNX2.

LncRNA PCBP1-AS1 induces osteoporosis by sponging miR-126-5p/PAK2 axis

“…32 In addition, miR-205-5p inhibits osteogenic differentiation of hBMSCs by regulating RUNX2, facilitating the development of OP. 33 miR-126-5p, an intronic miRNA, has been identified as a tumour suppressor in a variety of human cancer types, including cervical, breast, Fig. 7 The mechanism of PCBP1 Antisense RNA 1 (PCBP1-AS1)/microRNA (miR)-126-5p/group I Pak family member p21-activated kinase 2 (PAK2) axis in osteoporosis.…”

MiR-152-5p suppresses osteogenic differentiation of mandible mesenchymal stem cells by regulating ATG14-mediated autophagy

“…OP impairs not only the tooth [ 42 ] and periodontal tissues [ 43 ] but also implantation treatment, especially, causing marginal bone loss around implants [ 44 ]. Recently, mounting reports have proved that miRNAs have an effect on osteogenic differentiation of mesenchymal stem cells through transcriptional activation or inhibition of osteogenesis-related genes [ 45 ] [ 46 ] or the genes in some signal pathway [ 19 ]. However, we demonstrated that downregulation of miR-152-5p regulates osteogenic differentiation of OVX MMSCs-M via promoting autophagy.…”

MicroRNA-loaded biomaterials for osteogenesis

“…Runx2 is the main regulator of osteogenesis, which will promote the expression of osteopontin (OPN) and osteocalcin (OCN) ( Kureel et al, 2017 ; Hu et al, 2020 ; Marycz et al, 2021 ). Some miRNAs directly target RUNX2 to regulate the BMP/SMAD signaling pathway and interfere with other signaling pathways ( Zhang et al, 2017c ; Huang et al, 2020a ). MiR-133a/135a/93-3p targets Runx2 mRNA to inhibit the differentiation process of osteoblast cells ( Zhang et al, 2017a ; Kureel et al, 2017 ).…”