Identification and functional analysis of long non‐coding RNAs in the synovial membrane of osteoarthritis patients

Abstract

Osteoarthritis (OA), the most common chronic joint disease in the elderly, has become a significant economic burden for families and societies worldwide. Although treatments are continually improving, current drugs only target joint pain, with no effective therapies modifying OA progression. Long noncoding RNAs (lncRNAs), which have received increasing attention in recent years, are abnormally expressed in OA cartilage. In the present study, weighted coexpression network analysis (WGCNA) was applied to identify modules related to certain OA clinical traits. In total, 4404 coding genes and 161 lncRNAs were differentially expressed based on two OA expression profile data sets and normal control samples. Subsequently, 11 independent modules were acquired, and the green module, with a total of 49 hub genes, was identified as the most relevant to OA. These hub genes were validated using the GSE12021 data set. There was only one lncRNA among the hub genes, namely, NONHSAG034351. Thus, we further explored the function of NONHSAG034351‐related genes in the network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that NONHSAG034351‐associated genes are involved in the response to lipopolysaccharide, angiogenesis, tumour necrosis factor (TNF) signalling, and mitogen‐activated protein kinase (MAPK) signalling pathways. In conclusion, we identified modules through WGCNA related to OA clinical traits. NONHSAG034351, the only hub‐lncRNA, was downregulated in OA synovial tissue and might play a significant role in the pathological progression of this disease. Our findings have important clinical implications and could provide novel biomarkers that indicate the molecular mechanisms of OA and act as potential therapeutic targets. Significance of this study Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in osteoarthritis (OA), which is the most common chronic joint disease among the elderly. In the present study, we report the expression profiles of lncRNAs in OA and the identification of modules through WGCNA related to OA clinical traits. NONHSAG034351, the only hub‐lncRNA identified to be downregulated in the synovial tissue of OA patients, might play a significant role in the pathological progression of OA. Furthermore, our findings provide novel biomarkers associated with the molecular mechanisms underlying OA pathogenesis, thus implying potential therapeutic targets with important clinical implications.

Comprehensive analysis of lncRNA and mRNA based on expression microarray profiling reveals different characteristics of osteoarthritis between Tibetan and Han patients

“…It has been reported that some risk pathways such as TGF-β signaling pathway and inflammatory bowel disease and risk biological processes such as chondrocyte differentiation and regulation of cartilage development are involved in the OA pathology [ 56 ]. Functional analysis of lncRNA in the synovial membrane of osteoarthritis patients revealed that lipopolysaccharide, angiogenesis, tumor necrosis factor (TNF) signaling, and mitogen-activated protein kinase (MAPK) signaling pathways might contribute to OA development [ 57 ]. Interestingly, our GO and KEGG analysis showed that several unreported processes such as muscle cell proliferation, cell-cell adhesion, and chemokine ligand 2 production and signaling pathways including Hippo signaling pathway, Wnt signaling pathway, and Ras signaling pathway were particularly identified in Tibetan OA patients compared to the Chinese Han OA patients.…”

Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

“…WGCNA is a systematic biological algorithm [26], which is used to reveal the association between genes and clinical phenotypes [47]. It has been widely used to identified potential biomarkers for Alzheimer's disease [48], breast cancer [49], and osteoarthritis [50]. In this paper, WGCNA identified 7 modules.…”

Osteoarthritis year in review: genetics, genomics, epigenetics

“…Long Intergenic Non-Coding RNAs. Studies this year identified differentially expressed lncRNA in OA synovium [63], and long-intergenic non-coding RNA in hip OA cartilage [64].…”