The Roles of SNHG Family in Osteoblast Differentiation

Abstract

Small nucleolar RNA host genes (SNHGs), members of long-chain noncoding RNAs (lncRNAs), have received increasing attention regarding their roles in multiple bone diseases. Studies have revealed that SNHGs display unique expression profile during osteoblast differentiation and that they could act as promising biomarkers of certain bone diseases, such as osteoporosis. Osteogenesis of mesenchymal stem cells (MSCs) is an important part of bone repair and reconstruction. Moreover, studies confirmed that the SNHG family participate in the regulation of osteogenic differentiation of MSCs in part by regulating important pathways of osteogenesis, such as Wnt/β-catenin signaling. Based on these observations, clarifying the SNHG family's roles in osteogenesis (especially in MSCs) and their related mechanisms would provide novel ideas for possible applications of lncRNAs in the diagnosis and treatment of bone diseases. After searching, screening, browsing and intensive reading, we uncovered more than 30 papers related to the SNHG family and osteoblast differentiation that were published in recent years. Here, our review aims to summarize these findings in order to provide a theoretical basis for further research.

Keywords: SNHG family; bone diseases; mesenchymal stem cells; osteoblast differentiation.

Figure 1

The expression of SNHG8 increased in osteogenic medium. For the induction of osteoblast differentiation, PDLSCs were cultured in osteogenic medium (OM), which was composed of growth medium supplemented with b-glycerophosphate (10 mM), dexamethasone (100 nM) and vitamin C (200 mM). The relative mRNA expression of (A) alkaline phosphatase (ALP), (B) osteocalcin (OCN) and (C) small nucleolar RNA host gene 8 (SNHG8) was measured by qRT-PCR on the second day of osteogenic induction. Three repeated experiments were conducted. Data are presented as the mean ± SD, * p < 0.05, ** p < 0.01.

Figure 2

Schematic illustration of lncRNA GAS5 regulating osteogenesis of BMSCs by directly binding to protein UPF1. GAS5 binds to the HD region of UPF1 specifically, which results in binding of UPF1 and SMAD7 (mRNA). After binding to UPF1, SMAD7 (mRNA) degrades. As an inhibitor of the SMAD 1/5/8 pathway, degradation of SMAD7 promotes activation of SMAD 1/5/8 pathway and ultimately promotes osteoblast differentiation of BMSCs.

Figure 3

Schematic illustration of lncRNA DANCR regulating osteoblast differentiation of MSC by directly binding to protein FOXO1. Through unknown mechanisms, DANCR inhibits FOXO1 expression. Additionally, DANCR directly binds to FOXO1 and promotes Skp2-mediated ubiquitination of FOXO1, which further reduces FOXO1 expression. FOXO1, a transcription factor, regulates proliferation, differentiation and apoptosis of osteoblasts. By decreasing FOXO1 expression, DANCR ultimately inhibits osteoblast differentiation of MSC. U.M., unknown mechanism.