LncRNA expression profiles and the negative regulation of lncRNA-NOMMUT037835.2 in osteoclastogenesis

Abstract

Bone is a rigid and dynamic organ that continuously undergoes remodeling and repair. The balance between osteoblastic bone formation and osteoclastic bone resorption is essential for normal bone homeostasis. Osteoclasts are giant multinucleated cells derived from the monocyte/macrophage hematopoietic lineage and are regulated by various cytokines. Long non-coding (lnc) RNAs are known to regulate many biological processes in the skeletal system in both normal and diseased states; however, the lncRNA-mediated regulation of osteoclastogenesis has not been extensively studied. Hence, in the present study, we performed microarray analysis of lncRNAs expressed during different stages of osteoclast differentiation and fusion. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed the biological functions of target genes of lncRNAs that were specifically up- or downregulated at the different stages. Microarray and bioinformatic prediction results were used to generate co-expression networks of lncRNAs-mRNAs and lncRNAs-transcription factors. Based on the analysis, we identified one lncRNA, NONMMUT037835.2, which plays an important role during osteoclastogenesis. Upregulation of lncRNA-NONMMUT037835.2 inhibited osteoclastic differentiation, whereas downregulation of lncRNA-NONMMUT037835.2 promoted osteoclast formation and fusion. Our study also indicated that lncRNA-NOMMUT037835.2 might regulated osteoclastogenesis through negatively regulating RANK expression and inhibiting NF-κB/MAPK signaling pathway. Our results lead to a better understanding of the molecular mechanisms and provided a theoretical basis for developing therapeutic agents for diseases related to dysregulation of bone homeostasis.

Keywords: Expression profiles; Function prediction; LncRNA-NONMMUT037835.2; LncRNAs; Osteoclastogenesis; RANK.