In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 16, No. 5 ( 2022-5-2), p. e0010379-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0010379
DOI:
10.1371/journal.pntd.0010379.g001
DOI:
10.1371/journal.pntd.0010379.g002
DOI:
10.1371/journal.pntd.0010379.g003
DOI:
10.1371/journal.pntd.0010379.g004
DOI:
10.1371/journal.pntd.0010379.t001
DOI:
10.1371/journal.pntd.0010379.t002
DOI:
10.1371/journal.pntd.0010379.t003
DOI:
10.1371/journal.pntd.0010379.t004
DOI:
10.1371/journal.pntd.0010379.s001
DOI:
10.1371/journal.pntd.0010379.s002
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2429704-5
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