Osteoclast-derived exosomes influence osteoblast differentiation in osteoporosis progression via the lncRNA AW011738/ miR-24-2-5p/ TREM1 axis - 21/08/24
, Binyu Wang a, 1 , Hongtao Chen c, 1 , Xiao Yu a , Xiaojian Cao a, ⁎ , Hongxiu Zhang b, ⁎ Abstract |
Aims |
To investigate the molecular mechanism of osteoclast-derived exosomes in osteoporosis.
Main methods |
RANKL induced osteoclast model was screened for significantly differentially expressed lncRNAs and mRNAs by whole RNA sequencing. Exosomes were characterized using electron microscopy, western blotting and nanosight. Overexpression or knockdown of AW011738 was performed to explore its function. The degree of osteoporosis in an osteoporosis model was assessed by mirco-CT. The osteoclast model, osteoblast differentiation ability and the molecular mechanism of lncRNA AW011738/miR-24-2-5p/TREM1 axis in osteoporosis were assessed by dual luciferase reporter gene assay, Western blotting (WB), immunofluorescence and ALP staining. Bioinformatics was used to predict interactions of key osteoporosis-related genes with miRNAs, transcription factors, and potential drugs after upregulation of AW011738. To predict the protein-protein interaction (PPI) network associated with key genes, GO and KEGG analyses were performed on the key genes. The ssGSVA was used to predict changes in the immune microenvironment.
Key findings |
Osteoclast-derived exosomes containing lncRNA AW011738 decreased the osteogenesis-related markers and accelerated bone loss in OVX mice. Osteoclast (si-AW011738)-derived exosomes showed a significant increase in biomarkers of osteoblast differentiation in vitro compared to the si-NC group. As analyzed by mirco-CT, tail vein injected si-AW011738 OVX mice were less osteoporotic than the control group. AW011738 inhibited osteoblast differentiation by regulating TREM1 expression through microRNA. Meanwhile, overexpression of miR-24-2-5p inhibited TREM1 expression to promote osteoblast differentiation.
Significance |
Osteoclast-derived exosomes containing lncRNA AW011738 inhibit osteogenesis in MC3T3-E1 cells through the lncRNA AW011738/miR-24-2-5p/TREM1 axis and exacerbate osteoporosis in OVX mice.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Osteoclast-derived Exosomes transfer lncRNA AW011738 to osteoblasts. |
• | The lncRNA AW011738/miR-24-2-5p/TREM1 axis affects osteoblast proliferation and differentiation. |
• | AW011738 and TREM1 are potential therapeutic targets for osteoporosis. |
• | AW011738 triggers up- or down-regulation of several osteoporosis and inflammation-related key genes. |
• | Inhibition of AW011738 effectively prevents the progression of osteoporosis. |
Abbreviations : PPI, PMO, LncRNAs, DMEM, FBS, TRAP, QRT-PCR, PBS, TEM, DEGs, IFRGs, OSRGs, OVX, GO, BP, MF, CC, TFs, CTD, SsGSEA, TME, BV, BV/TV, BMD, Tb.Sp, Tb.N, PCA, WB, OPN, RBPs
Keywords : Osteoporosis, Exosomes, AW011738, TREM1, Osteogenic Differentiation
Plan
Vol 178
Article 117231- septembre 2024 Retour au numéro
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