Expression profile analysis of long non-coding RNA in skeletal muscle of osteoporosis by microarray and bioinformatics

Abstract

Background Osteoporosis (OP) is a condition featured by bone mass loss and bone tissue microarchitectural alterations due to impaired tissue homeostasis favoring excessive bone resorption versus deposition. The trigger of such an impairment and the downstream molecular pathways involved are yet to be clarified. Long non-coding RNA (lncRNA) plays a role in gene transcription, protein expression and epigenetic regulation; and altered expression results in immune or metabolism related desease development. To determine whether lncRNAs are involved in osteoporosis, we analyzed the expression profile of lncRNAs and mRNAs in osteoporosis. Method Three pairs of osteoporosis patients (OP group) and healthy people controls (NC group) were screened by microarray. Quantitative polymerase chain reaction (qRT-PCR) was performed to confirm dysregulated lncRNA expressions in 5 pairs of OP and NC group tissues samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to construct the lncRNA-mRNA co-expression network. Result Through co-expression analysis, differently expressed transcripts were divided into modules, and lncRNAs were functionally annotated. We further analyzed the clinical significance of crucial lncRNAs from modules in public data. Finally, the expression of five lncRNAs, CUST_44695_PI430048170-GeneSymbol:CTA-384D8.35;CUST_39447_PI430048170,CUST_73298_PI430048170,CUST_108340_PI430048170,CUST_118927_PI430048170,this four lncRNAs have not been annotation genes and have not found GeneSymbols, and by quantitative RT-PCR, which may be associated with osteoporosis patients’ overall survival. Conclusion Analysis of this study revealed that dysregulated lncRNAs and mRNAs in osteoporosis patients and health people controls could affect the immune or metabolism system and musculoskeletal cell differentiation. The biological functions of those lncRNAs need to be further validated.

Alterations in DNA methylation profiles in cancellous bone of postmenopausal women with osteoporosis

“…The mutation of PNPLA7 gene (rs3812499) is related to rheumatoid arthritis [23]. It is found that SCD is up-regulated in skeletal muscle tissues of patients with osteoporosis [24]. Moreover, high SCD activity significantly increases the risk for fracture in men [25].…”

Osteoporosis Is Characterized by Altered Expression of Exosomal Long Non-coding RNAs

“…Thus, we report the presence of a unique set of lncRNAs in the serum-derived exosomes with significant functional implications in osteoporosis. Although the function of the majority of lncRNAs remains to be elucidated, previous studies have indicated that lncRNAs may be involved in the pathogenesis of osteoporosis (Kung et al, 2013 ; Fei et al, 2018 ; Liu et al, 2019 ). We were also able to validate 11 differentially expressed lncRNAs by quantitative PCR using lncRNA specific primers ( Figure 8 ).…”

“…IncRNAs regulate gene expression by recruiting transcriptional factors, by acting on the RNA polymerase machinery or by sequestrating the microRNA that silence the mRNA expression (Dykes and Emanueli, 2017 ; Silva et al, 2019 ). A study by Liu et al ( 2019 ), reported that about 1,500 lncRNAs were differentially expressed in case of osteoporotic conditions out of which around 250 lncRNAs showed significant variation. Other studies also have indicated the roles of few long non-coding RNAs like lncRNA RP11-498C9, lncRNA XR111050, lncRNA ANCR in regulation of osteogenic gene expression (Li et al, 2019 ; Silva et al, 2019 ).…”

Characterization of Dysregulated lncRNA-Associated ceRNA Network Reveals Novel lncRNAs With ceRNA Activity as Epigenetic Diagnostic Biomarkers for Osteoporosis Risk

“…Another study by Seeliger et al (2014) also identified five freely circulating miRNAs associated with osteoporosis fractures. There is increasing evidence that lncRNAs also play important roles in the pathogenesis of osteoporosis (Peng et al, 2018;Feng et al, 2019;Liu et al, 2019). In this study, we obtained lncRNA profiles of osteoporosis patients by repurposing array probes on publicly available microarray data and performed genome-wide analysis for expression patterns of lncRNAs, miRNAs, and mRNAs between high-and low-BMD subjects.…”