A comprehensive analysis of the circRNA-miRNA-mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection.

Background Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. Methodology/principal findings Osteocytes may have a role through regulating the differentiatio...

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Bibliographic Details
Published in:PLOS Neglected Tropical Diseases
Main Authors: Zheng-Rong Gao, Qiong Liu, Jie Zhao, Ya-Qiong Zhao, Li Tan, Shao-Hui Zhang, Ying-Hui Zhou, Yun Chen, Yue Guo, Yun-Zhi Feng
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2022
Subjects:
Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Arctic
Online Access:https://doi.org/10.1371/journal.pntd.0010379
https://doaj.org/article/2527e83760db4c3198b7e488e29d8f1d
Description
Summary:Background Bone formation and loss are the characteristic clinical manifestations of leprosy, but the mechanisms underlying the bone remodeling with Mycobacterium leprae (M. leprae) infection are unclear. Methodology/principal findings Osteocytes may have a role through regulating the differentiation of osteogenic lineages. To investigate osteocyte-related mechanisms in leprosy, we treated osteocyte-like cell with N-glycosylated muramyl dipeptide (N.g MDP). RNA-seq analysis showed 724 differentially expressed messenger RNAs (mRNAs) and 724 differentially expressed circular RNA (circRNAs). Of these, we filtered through eight osteogenic-related differentially expressed genes, according to the characteristic of competing endogenous RNA, PubMed databases, and bioinformatic analysis, including TargetScan, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes. Based on these results, we built a circRNA-microRNA (miRNA)-mRNA triple network. Quantitative reverse-transcription polymerase chain reaction and western blots analyses confirmed decreased Clock expression in osteocyte-like cell, while increased in bone mesenchymal stem cells (BMSCs), implicating a crucial factor in osteogenic differentiation. Immunohistochemistry showed obviously increased expression of CLOCK protein in BMSCs and osteoblasts in N.g MDP-treated mice, but decreased expression in osteocytes. Conclusions/significance This analytical method provided a basis for the relationship between N.g MDP and remodeling in osteocytes, and the circRNA-miRNA-mRNA triple network may offer a new target for leprosy therapeutics.

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