Bone marrow stromal cells (BMSCs CD45^‐/CD44⁺/CD73⁺/CD90⁺) isolated from osteoporotic mice SAM/P6 as a novel model for osteoporosis investigation

Journal of Cellular and Molecular Medicine, Journal Year: 2021, Volume and Issue: 25(14), P. 6634 - 6651

Published: June 1, 2021

Abstract Available therapies aimed at treating age‐related osteoporosis are still insufficient. Therefore, designing reliable in vitro model for the analysis of molecular mechanisms underlying senile is highly required. We have isolated and characterized progenitor cells from bone marrow (BMSCs) osteoporotic mice strain SAM/P6 (BMSC ). The cytophysiology BMSC was first time compared with BMSCs healthy BALB/c Characterization included evaluation their multipotency, morphology determination specific phenotype. Viability cultures determined reference to apoptosis profile, metabolic activity, oxidative stress, mitochondrial membrane potential caspase activation. Additionally, expression relevant biomarkers RT‐qPCR. Obtained results indicated that show typical phenotype mesenchymal stromal (CD44+, CD73+, CD90+) do not express CD45. Further, were by deteriorated decreased activity increased occurrence, accompanied elevated stress mitochondria depolarisation. transcriptome analyses showed distinguished lowered molecules crucial proper osteogenesis, including Coll‐1 , Opg Opn . However, Trap DANCR1 miR‐124‐3p significantly up‐regulated. present features disturbed metabolism could serve as appropriate investigation age‐dependent osteoporosis.

Language: Английский

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DNA-methylation-induced silencing of DIO3OS drives non-small cell lung cancer progression via activating hnRNPK-MYC-CDC25A axis

Molecular Therapy — Oncolytics, Journal Year: 2021, Volume and Issue: 23, P. 205 - 219

Published: Oct. 1, 2021

DNA methylation is a class of epigenetic modification manner, which responsible for the inactivation various tumor suppressors. Recently, long non-coding RNAs (lncRNAs) were revealed to be implicated in variety malignancies, including non-small cell lung cancer (NSCLC). However, contributions lncRNAs DNA-methylation-induced oncogenic effects NSCLC remain largely unknown. In this study, we identified DNA-methylation-repressed lncRNA DIO3 opposite strand upstream RNA (DIO3OS) NSCLC. DIO3OS downregulated NSCLC, and its low expression related poor prognosis. Ectopic repressed growth motility promoted apoptosis vitro. also tumorigenesis metastasis vivo. knockdown exhibited biological effects. competitively bound heterogeneous nuclear ribonucleoprotein K (hnRNPK), binding hnRNPK MYC mRNA, reduced promoting roles on transcription translation, led repression therefore remarkably decreased CDC25A, downstream target MYC. Additionally, depletion blocked tumor-suppressive conclusion, these findings as an important protective factor against via modulating hnRNPK-MYC-CDC25A axis.

Language: Английский

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Role of Bioinformatics in Non-coding RNA Analysis

Advances in Bioinformatics, Journal Year: 2024, Volume and Issue: unknown, P. 113 - 136

Published: Jan. 1, 2024

The transcriptome, comprising RNA molecules expressed in cells or tissues, is predominantly composed of non-coding RNAs (ncRNAs), which has most the region genome humans. classification ncRNAs includes housekeeping and regulatory ncRNAs, with latter encompassing long-ncRNAs (lncRNAs), microRNAs (miRNAs), small interfering (siRNAs). These including lncRNAs, play a crucial role various levels gene regulation, like transcription, processing, translation, chromatin modification. By interacting RNA, DNA, proteins, lncRNAs influence structure localization activity protein complexes processing. study presents both challenges opportunities, as they exhibit complex sequence structural characteristics. application bioinformatics highlights how computational methods have contributed to prediction identification novel target prediction, evolutionary analysis, functional construction networks. This chapter briefly discusses databases tools that aid analysis interpretation ncRNA data, LncTarD, LnCeVar, MirGeneDB, miRTarBase, SEAweb, DIANA-LncBase, miRPathDB, RNAInter, oRNAment, miRDB, ENCORI, NPInter, etc. resources provide valuable information on interactions, targets, functions, enabling researchers explore world ncRNAs.

Language: Английский

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DANCR Mediates the Rescuing Effects of Sesamin on Postmenopausal Osteoporosis Treatment via Orchestrating Osteogenesis and Osteoclastogenesis

Nutrients, Journal Year: 2021, Volume and Issue: 13(12), P. 4455 - 4455

Published: Dec. 13, 2021

As one of the leading causes bone fracture in postmenopausal women and older men, osteoporosis worldwide is attracting more attention recent decades. Osteoporosis a common disease mainly resulting from an imbalance formation resorption. Pharmaceutically active compounds that both activate osteogenesis, while repressing osteoclastogenesis hold potential being therapeutic medications for treatment. In present study, sesamin, bioactive ingredient derived seed Sesamum Indicum, was screened out compound library shown to exhibit dual-regulating functions on these two processes. Sesamin demonstrated promote osteogenesis by upregulating Wnt/β-catenin, via downregulating NF-κB signaling . Furthermore, DANCR found be key regulator sesamin-mediated resorption ovariectomy (OVX)-induced osteoporotic mouse model, sesamin could rescue OVX-induced loss impairment. The increased serum level caused OVX also downregulated upon conclusion, our results demonstrate plays dual-functional role activation de-activation DANCR-dependent manner, suggesting it may possible medication candidate patients with elevated DNACR expression levels.

Language: Английский

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Oncogenic Long Noncoding RNAs in Prostate Cancer, Osteosarcoma, and Metastasis

Biomedicines, Journal Year: 2023, Volume and Issue: 11(2), P. 633 - 633

Published: Feb. 20, 2023

Prostate cancer (PC) is a common malignancy and one of the leading causes cancer-related death in men worldwide. Osteosarcoma (OS) most bone cancer, representing 20–40% all cases. Cancer metastasis process by which malignant tumor cells detach from primary site via cascade processes migrate to secondary sites through blood circulation or lymphatic system colonize form tumors. PC has specific affinity based on “seed soil” theory; once reach bone, it becomes incurable. Several studies have identified long noncoding RNAs (lncRNAs) as potential targets for therapy diagnostic prognostic biomarkers. The dysregulation various lncRNAs been found types, including PC, OS, metastasis. However, mechanisms underlying lncRNA oncogenic activity progression are extremely complex remain incompletely understood. Therefore, understanding their role mechanism may help better manage treat this malignancy. aim review summarize current knowledge involvement

Language: Английский

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Assessment of Reference Genes Stability in Cortical Bone of Obese and Diabetic Mice

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2024, Volume and Issue: Volume 17, P. 1081 - 1091

Published: March 1, 2024

Bone, a pivotal structural organ, is susceptible to disorders with profound health implications. The investigation of gene expression in bone tissue imperative, particularly within the context metabolic diseases such as obesity and diabetes that augment susceptibility fractures. objective this study identify set internal control genes for analysis expression. This employs reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) assess tissue. We selected fourteen housekeeping assessed their stability cortical mouse models using four well-established algorithms (GeNorm, BestKeeper, NormFinder, comparative Delta Ct method). identified Rpl13a mostly stably expressed reference from (db/db), while Gapdh was found be most stable another model, KKAy mice. Additionally, Ef1a, Ppia, Rplp0, Rpl22 were alternative suitable normalizing models. These findings enhance RT-qPCR accuracy reliability, offering strategic guide select studying disorders.

Language: Английский

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Novel Nanohydroxyapatite (nHAp)-Based Scaffold Doped with Iron Oxide Nanoparticles (IO), Functionalized with Small Non-Coding RNA (miR-21/124) Modulates Expression of Runt-Related Transcriptional Factor 2 and Osteopontin, Promoting Regeneration of Osteoporotic Bone in Bilateral Cranial Defects in a Senescence-Accelerated Mouse Model (SAM/P6). PART 2

International Journal of Nanomedicine, Journal Year: 2021, Volume and Issue: Volume 16, P. 6049 - 6065

Published: Aug. 1, 2021

Healing of osteoporotic defects is challenging and requires innovative approaches to elicit molecular mechanisms promoting osteoblasts-osteoclasts coupling bone homeostasis.Cytocompatibility biocompatibility previously characterised nanocomposites, i.e Ca5(PO4)3OH/Fe3O4 (later called nHAp/IO) functionalised with microRNAs (nHAp/IO@miR-21/124) was tested. In vitro studies were performed using a direct co-culture system MC3T3-E1 pre-osteoblast 4B12 pre-osteoclasts. The analysis included determination nanocomposite influence on cultures morphology (confocal imaging), viability metabolic activity (Alamar Blue assay). Pro-osteogenic signals identified at mRNA, miRNA protein level RT-qPCR, Western blotting immunocytochemistry. Biocompatibility biomaterials tested bilateral cranial defect senescence-accelerated mouse model, ie SAM/P6 Balb/c. effect biomaterial the process healing monitored microcomputed tomography.The nanocomposites promoted survival metabolism cells, as well enhanced functional differentiation pre-osteoblasts in co-cultures Differentiation driven by nHAp/IO@miR-21/124 manifested improved extracellular matrix up-regulation pro-osteogenic transcripts, late osteogenesis markers. triggered model mice replaced Balb/c mice.This study demonstrates that novel nHAp/IO can serve platform for therapeutic delivery. Obtained signals, decreasing osteoclasts differentiation, simultaneously improving osteoblasts their transition toward pre-osteocytes mineralisation. proposed scaffold be an effective interface situ regeneration bone, especially elderly patients.

Language: Английский

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Long Non-coding RNAs in Traumatic Brain Injury Accelerated Fracture Healing

Frontiers in Surgery, Journal Year: 2021, Volume and Issue: 8

Published: June 4, 2021

It is commonly observed that patients with bone fracture concomitant traumatic brain injury (TBI) had significantly increased healing, but the underlying mechanisms were not fully revealed. Long non-coding RNAs (lncRNAs) are known to play complicated roles in homeostasis, their role TBI accelerated was rarely reported. The present study designed determine of lncRNAs via transcriptome sequencing and further bioinformatics analyses. Blood samples from three fracture-only patients, healthy controls harvested subsequently subjected lncRNA sequencing. Differentially expressed genes identified, pathway enrichment performed by Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) analysis. High-dimensional data visualization self-organizing map (SOM) machine learning applied interpret data. An xCell method then used predict cellular behavior all based on gene expression profiles, an lncRNA–cell interaction network generated. A total 874 differentially which about 26% lncRNAs. Those identified mainly enriched TBI-related damage repair-related pathways. SOM analyses revealed those could be divided into major module implications transcriptional regulation immune-related signal pathways, promote us explore behaviors We have predicted basophils, CD8+ T effector memory cells, B naïve cells downregulated, while microvascular endothelial upregulated Fr/TBI group, lowest highest, respectively. ENSG00000278905, ENSG00000240980, ENSG00000255670, ENSG00000196634 most related changes behavior. has for first time several critical may participate potentially regulating cytotoxic cells.

Language: Английский

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(In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers

Cancers, Journal Year: 2021, Volume and Issue: 13(20), P. 5040 - 5040

Published: Oct. 9, 2021

Rare ovarian cancers (ROCs) are OCs with an annual incidence of fewer than 6 cases per 100,000 women. They affect women all ages, but due to their low and the potential clinical inexperience in management, there can be a delay diagnosis, leading poor prognosis. The underlying causes for these tumors varied, generally, arise alterations gene/protein expression cellular processes that regulate normal proliferation its checkpoints. Dysregulation lead cancer includes gene mutations, epimutations, non-coding RNA (ncRNA) regulation, posttranscriptional posttranslational modifications. Long (lncRNA) defined as transcribed molecules, more 200 nucleotides length which not translated into proteins. through several mechanisms therefore add another level complexity regulatory affecting tumor development. Since few studies have been performed on ROCs, this review we summarize action lncRNA OC, emphasis ROCs.

Language: Английский

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Pulsed Electromagnetic Field Promotes Bone Anabolism in Postmenopausal Osteoporosis through the miR-6976/BMP/Smad4 Axis

Journal of Tissue Engineering and Regenerative Medicine, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 13

Published: June 3, 2023

Insufficient bone formation is the key reason for imbalance of metabolism and one main mechanisms occurrence deterioration postmenopausal osteoporosis (PMOP). Accumulating evidence has demonstrated that pulsed electromagnetic field (PEMF), as a physiotherapy, can treat by promoting osteogenic differentiation in osteoblasts. However, little known about its mechanisms. In vivo, ovariectomized mice were administered PEMF 4 weeks, skeletal analysis was conducted. vitro, hydrogen peroxide-treated mouse osteoblast precursor cells with or without intervention subjected to testing miRNA microarrays. The potential target miRNAs validated, followed gene expression assays further clarify their regulatory relationships pathways. We found reduced loss promoted via downregulation miR-6976-5p. Mechanistically, miR-6976-5p enhanced nuclear transport phosphorylated Smad1/5/9 upregulating Smad4, thereby activating BMP/Smad pathway. Additionally, administration inhibitors successfully antagomirs protected mass vivo. mimics agomirs acted opposite way. These results provide alleviates estrogen deficiency-induced osteoblastic progenitor maintaining shed light on involved, which may option clinical application PMOP.

Language: Английский

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