A comprehensive analysis of the circRNA-miRNA-mRNA network in osteocyte-like cell associated with Mycobacterium leprae infection.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
27
08
2021
accepted:
31
03
2022
revised:
12
05
2022
pubmed:
3
5
2022
medline:
18
5
2022
entrez:
2
5
2022
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 35500036
doi: 10.1371/journal.pntd.0010379
pii: PNTD-D-21-01278
pmc: PMC9098081
doi:
Substances chimiques
MicroRNAs
0
RNA, Circular
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0010379Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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