Mechanism of dexmedetomidine regulating osteogenesis-angiogenesis coupling through the miR-361-5p/VEGFA axis in postmenopausal osteoporosis

Wang, Ziyi; Ge, Xinghua; Wang, Yan; Liang, Yunjie; Shi, Huifang; Zhao, Tao

doi:10.1016/j.lfs.2021.119273

Cited by 13 publications

(9 citation statements)

References 35 publications

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“…The features of senile osteoporosis, including decreased bone mass, degenerative bone quality and impaired vessel formation, are being validated by multiple animal models [ 21 ]. A concurrent hotspot in research for alleviating degenerative osteogenesis–angiogenesis coupling is the investigation of gene therapy based on the underlying pathogenic mechanisms [ 22 , 23 ]. HIF1α is one of the essential factors in mediating bone-vessel crosstalk.…”

Section: Discussionmentioning

confidence: 99%

A dual role of HIF1α in regulating osteogenesis–angiogenesis coupling

et al. 2022

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Objectives The hypoxia-inducible factor 1-α (HIF1α), a key molecule in mediating bone-vessel crosstalk, has been considered a promising target for treating osteoporosis caused by gonadal hormones. However, senile osteoporosis, with accumulated senescent cells in aged bone, has a distinct pathogenesis. The study aimed at revealing the unknown role of HIF1α in aged bone, thus broadening its practical application in senile osteoporosis. Materials and methods Femurs and tibias were collected from untreated mice of various ages (2 months old, 10 months old, 18 months old) and treated mice (2 months old, 18 months old) underwent 4-w gavage of 2-methoxyestradiol (a kind of HIF1α inhibitor). Bone-vessel phenotypes were observed by microfil infusion, micro-CT and HE staining. Markers of senescence, osteogenesis, angiogenesis, oxidative stress and expression of HIF1α were detected by senescence β-galactosidase staining, qRT-PCR, western blot and immunostaining, respectively. Furthermore, bone mesenchymal stem cells from young mice (YBMSCs) and aged mice (ABMSCs) were transfected by knockout siRNA and overexpression plasmid of HIF1α. Senescence β-galactosidase staining, Cell Counting Kit-8, transwell assay, alkaline phosphatase staining, alizarin red-S staining and angiogenesis tests were utilized to assess the biological properties of two cell types. Then, Pifithrin-α and Nutlin-3a were adopted to intervene p53 of the two cells. Finally, H2O2 on YBMSCs and NAC on ABMSCs were exploited to change their status of oxidative stress to do a deeper detection. Results Senescent phenotypes, impaired osteogenesis–angiogenesis coupling and increased HIF1α were observed in aged bone and ABMSCs. However, 2-methoxyestradiol improved bone-vessel metabolism of aged mice while damaged that of young mice. Mechanically, HIF1α showed opposed effects in regulating the cell migration and osteogenesis–angiogenesis coupling of YBMSCs and ABMSCs, but no remarked effect on the proliferation of either cell type. Pifithrin-α upregulated the osteogenic and angiogenic markers of HIF1α-siRNA-transfected YBMSCs, and Nutlin-3a alleviated those of HIF1α-siRNA-transfected ABMSCs. The HIF1α-p53 relationship was negative in YBMSCs and NAC-treated ABMSCs, but positive in ABMSCs and H2O2-treated YBMSCs. Conclusion The dual role of HIF1α in osteogenesis–angiogenesis coupling may depend on the ROS-mediated HIF1α-p53 relationship. New awareness about HIF1α will be conducive to its future application in senile osteoporosis.

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Section: Discussionmentioning

confidence: 99%

A dual role of HIF1α in regulating osteogenesis–angiogenesis coupling

et al. 2022

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“…Consistently, the functions of some of these miRNAs and genes in osteoporosis have been investigated. Z. Wang et al exhibited that miR-361 has been upregulated in osteoporosis patients [ 23 ]. MiR-484 has been discovered to positively associate with bone mineral density in in femoral bone [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

miRNA‐Gene Interaction Network Construction Strategy to Discern Promising Traditional Chinese Medicine against Osteoporosis

Xiahatai

Han

2022

BioMed Research International

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Osteoporosis is a widespread bone disease that affects million cases annually. The underlying mechanisms behind the progress of osteoporosis remain enigmatic, which limits detections of biomarkers and therapeutic targets. Hence, this study was aimed at exploring hub molecules to better understand the mechanism of osteoporosis development and discover the traditional Chinese medicine potential drugs for osteoporosis. miRNA and gene expression profiles were downloaded from Gene Expression Omnibus (GEO). Weighted correlation network analysis (WGCNA) was used to identify the key modules for osteoporosis. DIANA Tools was applied to perform pathway enrichment. A miRNA-gene interaction network was constructed, and hub miRNAs and genes were distinguished using Cytoscape software. Receiver operating characteristic (ROC) curves of hub miRNAs and genes were plotted, and correlations with hub genes and osteoporosis-associated factors were evaluated. Potential drugs for osteoporosis in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were screened, and molecular docking models between these drugs and target genes were showed by AutoDock tools. Two hub modules, 1 miRNA module and 1 gene module, were identified to be the most strongly correlated with osteoporosis by using WGCNA. Then, 3 KEGG pathways including focal adhesion, PI3K-Akt signaling pathway, and gap junction were shared pathways enriched with the miRNAs and genes screened out by WGCNA and differential expression analyses. Finally, after constructing a miRNA-gene interaction network, 6 hub miRNAs (hsa-miR-18b-3p, hsa-miR-361-3p, hsa-miR-484, hsa-miR-519e-5p, hsa-miR-940, and hsa-miR-1275) and 6 hub genes (THBS1, IFNAR2, ARHGAP5, TUBB2B, FLNC, and NTF3) were detected. ROC curves showed good performances of miRNAs and genes for osteoporosis. Correlations with hub genes and osteoporosis-associated factors suggested implicational roles of them for osteoporosis. Based on these hub genes, 3 natural compounds (kainic acid, uridine, and quercetin), which were the active ingredients of 192 herbs, were screened out, and a target-compound-herb network was extracted using TCMSP. Molecular docking models of kainic acid-NTF3, uridine-IFNAR2, and quercetin-THBS1 were exhibited with AutoDock tools. Our study sheds light on the pathogenesis of osteoporosis and provides promising therapeutic targets and traditional Chinese medicine drugs for osteoporosis.

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“…Interestingly, each MRI phenotype demonstrated the presence of a specific miRNA whose function is involved in blood–brain barrier (BBB) pathology. Specifically, miR-22–3p, miR361–5p, and miR-345–5p, all involved in the angiogenesis process [ 34 , 35 , 36 ], were the most valid differentiators of the MRI phenotypes [ 37 ]. However, it must be underlined that, on this issue, there are conflicting results, heterogeneity of data, and lack of replication and that there is still a lot of work in progress regarding the mechanism of miRNA networks and their targets.…”

Section: Angiogenesis In Multiple Sclerosismentioning

confidence: 99%

Angiogenesis and Multiple Sclerosis Pathogenesis: A Glance at New Pharmaceutical Approaches

Gentile

Muto

Lus

et al. 2022

JCM

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Multiple sclerosis is a chronic disease of the central nervous system characterized by demyelination and destruction of axons. The most common form of the disease is the relapsing-remitting multiple sclerosis in which episodic attacks with typical neurological symptoms are followed by episodes of partial or complete recovery. One of the underestimated factors that contribute to the pathogenesis of multiple sclerosis is excessive angiogenesis. Here, we review the role of angiogenesis in the onset and in the development of the disease, the molecular mechanisms underlying angiogenesis, the current therapeutic approaches, and the potential therapeutic strategies with a look at natural compounds as multi-target drugs with both neuroprotective and anti-angiogenic properties.

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Mechanism of dexmedetomidine regulating osteogenesis-angiogenesis coupling through the miR-361-5p/VEGFA axis in postmenopausal osteoporosis

Cited by 13 publications

References 35 publications

A dual role of HIF1α in regulating osteogenesis–angiogenesis coupling

A dual role of HIF1α in regulating osteogenesis–angiogenesis coupling

miRNA‐Gene Interaction Network Construction Strategy to Discern Promising Traditional Chinese Medicine against Osteoporosis

Angiogenesis and Multiple Sclerosis Pathogenesis: A Glance at New Pharmaceutical Approaches

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