Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3772 - 3772

Published: Feb. 14, 2023

Osteoporosis is characterized by the alteration of bone homeostasis due to an imbalance between osteoclastic resorption and osteoblastic formation. Estrogen deficiency causes loss postmenopausal osteoporosis, pathogenesis which also involves oxidative stress, inflammatory processes, dysregulation expression microRNAs (miRNAs) that control gene at post-transcriptional levels. Oxidative increase in reactive oxygen species (ROS), proinflammatory mediators altered levels miRNAs enhance osteoclastogenesis reduce osteoblastogenesis through mechanisms involving activation MAPK transcription factors. The present review summarizes principal molecular involved role ROS cytokines on osteoporosis. Moreover, it highlights interplay among miRNA levels, state. In fact, ROS, activating transcriptional factors, can affect expression, regulate production processes. Therefore, should help identifying targets for development new therapeutic approaches osteoporotic treatment improve quality life patients.

Language: Английский

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Long Non-coding RNAs and MicroRNAs Interplay in Osteogenic Differentiation of Mesenchymal Stem Cells

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: April 9, 2021

Long non-coding RNAs (lncRNAs) have gained great attention as epigenetic regulators of gene expression in many tissues. Increasing evidence indicates that lncRNAs, together with microRNAs (miRNAs), play a pivotal role osteogenesis. While miRNA action mechanism relies mainly on miRNA-mRNA interaction, resulting suppressed expression, lncRNAs affect mRNA functionality through different activities, including interaction miRNAs. Recent advances RNA sequencing technology improved knowledge into the molecular pathways regulated by and This review reports recent miRNAs roles key osteogenic differentiation. Specifically, we described herein discoveries lncRNA-miRNA crosstalk during differentiation mesenchymal stem cells (MSCs) derived from bone marrow (BM), well other anatomical regions. The deep understanding connection between will strongly improve mechanisms growth development, ultimately leading to discover innovative diagnostic therapeutic tools for disorders diseases.

Language: Английский

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Regulatory mechanisms of circular RNAs during human mesenchymal stem cell osteogenic differentiation

Theranostics, Journal Year: 2023, Volume and Issue: 14(1), P. 143 - 158

Published: Nov. 15, 2023

Human osteogenic differentiation is a complex and well-orchestrated process which involves plethora of molecular players cellular processes.A growing number studies have underlined that circular RNAs (circRNAs) play an important regulatory role during human differentiation.CircRNAs are single-stranded, covalently closed non-coding RNA molecules acquiring increased attention as epigenetic regulators gene expression.Given their intrinsic high conformational stability, abundance, specificity, circRNAs can undertake various biological activities in order to regulate multiple processes, including differentiation.The most recent evidence indicates control osteogenesis by preventing the inhibitory activity miRNAs on downstream target genes, using competitive endogenous mechanism.The aim this review draw currently known mechanisms differentiation.Specifically, we provide understanding advances research conducted mesenchymal stem cell types importance regulating osteogenesis.A comprehensive underlying circRNA will improve knowledge processes bone growth, resulting potential development novel preclinical clinical discovery diagnostic therapeutic tools for disorders.

Language: Английский

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MiR-21-5p regulates the dynamic of mitochondria network and rejuvenates the senile phenotype of bone marrow stromal cells (BMSCs) isolated from osteoporotic SAM/P6 mice

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 29, 2023

Abstract Background Progression of senile osteoporosis is associated with deteriorated regenerative potential bone marrow-derived mesenchymal stem/stromal cells (BMSCs). According to the recent results, senescent phenotype osteoporotic strongly correlates impaired regulation mitochondria dynamics. Moreover, due ageing population and growing incidence, more efficient methods concerning BMSCs rejuvenation are intensely investigated. Recently, miR-21-5p was reported play a vital role in turnover, but its therapeutic mechanisms progenitor delivered from patients remain unclear. Therefore, goal this paper investigate for first time process mitochondrial network stemness restoration using unique model isolated SAM/P6 mice model. Methods were healthy BALB/c mice. We analysed impact on expression crucial markers related cells’ viability, reconstruction autophagy progression. Further, we established homeostasis, as well defined composition extracellular matrix osteogenic cultures. The miR-21 vivo also investigated critical-size cranial defect by computed microtomography SEM–EDX imaging. Results MiR-21 upregulation improved viability drove dynamics evidenced intensification fission processes. Simultaneously, enhanced differentiation increased Runx-2 downregulated Trap , calcification matrix. Importantly, analyses indicated greater ratio newly formed tissue after application, upregulated content calcium phosphorus within site. Conclusions Our results demonstrate that regulates fusion processes facilitates BMSCs. At same time, it enhances RUNX-2, while reduces TRAP accumulation phenotype. may bring novel molecular strategy diagnostics treatment.

Language: Английский

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Nanohydroxyapatite (nHAp) Doped with Iron Oxide Nanoparticles (IO), miR-21 and miR-124 Under Magnetic Field Conditions Modulates Osteoblast Viability, Reduces Inflammation and Inhibits the Growth of Osteoclast – A Novel Concept for Osteoporosis Treatment: Part 1

International Journal of Nanomedicine, Journal Year: 2021, Volume and Issue: Volume 16, P. 3429 - 3456

Published: May 1, 2021

Osteoporosis results in a severe decrease the life quality of many people worldwide. The latest data shows that number osteoporotic fractures is becoming an increasing international health service problem. Therefore, new kind controllable treatment methods for extensively desired. For reason, we have manufactured and evaluated nanohydroxyapatite (nHAp)-based composite co-doped with iron oxide (IO) nanoparticles. biomaterial was used as matrix controlled delivery miR-21-5p miR-124-3p, which proven impact on bone cell metabolism.The nanocomposite Ca5(PO4)3OH/Fe3O4 (later called nHAp/IO) obtained by wet chemistry method functionalised microRNAs (nHAp/IO@miR-21/124). Its physicochemical characterization performed using XRPD, FT-IR, SEM-EDS HRTEM SAED methods. modulatory effect tested vitro murine pre-osteoblasts MC3T3-E1 pre-osteoclasts 4B12. Moreover, anti-inflammatory effects were analysed model LPS-treated macrophages RAW 264.7. We cells' viability, mitochondria membrane potential oxidative stress under magnetic field (MF+) without (MF-). supplemented RT-qPCR Western blot assays to evaluate expression profile master regulators indicated pro-osteogenic nHAp/IO@miR-21/124 enhanced exposure MF. osteogenesis guided presence associated increased metabolism progenitor cells activation osteogenic markers (Runx-2, Opn, Coll-1). Simultaneously, decreased differentiation pre-osteoclastic 4B12 accompanied reduced CaII Ctsk. Obtained regulated viability showed immunomodulatory properties inhibiting inflammatory markers, ie, TNF-α, iNOs or IL-1β, LPS-stimulated 264.7 cells.We described first time concept osteoporosis based application. fabricated might proper regeneration bone, restoring balance between osteoblasts osteoclast.

Language: Английский

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Bioinformatic Tools for the Analysis and Prediction of ncRNA Interactions

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11397 - 11397

Published: Oct. 22, 2021

Noncoding RNAs (ncRNAs) play prominent roles in the regulation of gene expression via their interactions with other biological molecules such as proteins and nucleic acids. Although much our knowledge about how these ncRNAs operate different processes has been obtained from experimental findings, computational biology can also clearly substantially boost this by suggesting possible novel molecules. Computational predictions are thus used an alternative source new insights through a process mutual enrichment because information experiments continuously feeds into methods. The results turn shed light on that subsequently validated experimentally. This review describes latest advances databases, bioinformatic tools, silico strategies allow establishment or prediction ncRNAs, particularly miRNAs lncRNAs. ncRNA species described work have special emphasis those found humans, but is included.

Language: Английский

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LncRNA‐HHCP5 Regulates KLF5 in ceRNA and m6A Pathways to Inhibit the Progression of Osteoarthritis

International Journal of Rheumatic Diseases, Journal Year: 2025, Volume and Issue: 28(1)

Published: Jan. 1, 2025

ABSTRACT Background Osteoarthritis (OA) is one of the most common bone disorders and has a serious impact on quality life patients. LncRNA‐HCP5 (HCP5) downregulated in OA tissues. However, latent function regulatory mechanisms HCP5 are unclear. Methods In current study, IL‐1β‐induced C28/I2 cells were used to establish an vitro model OA. The expression cartilage tissue was detected by RT‐qPCR. Cell viability apoptosis assessed CCK‐8 Annexin V‐PI double staining. Western blotting employed detect protein MMP‐13 aggrecan. Results results showed that findings suggested cells. overexpression greatly enhanced proliferation cells, as well prevented cell degradation extracellular matrix (ECM). Besides, we have shown ceRNA regulates KLF5 sponging miR‐375. Furthermore, also regulated m6A regulation induced HCP5. Finally, miR‐375, modification inhibitor, inhibition reversed Conclusion summary, present study demonstrated HCP5/KLF5 axis inhibited progression osteoarthritis.

Language: Английский

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The Genetic and Biological Basis of Pseudoarthrosis in Fractures: Current Understanding and Future Directions

Diseases, Journal Year: 2025, Volume and Issue: 13(3), P. 75 - 75

Published: March 3, 2025

Pseudoarthrosis—the failure of normal fracture healing—remains a significant orthopedic challenge affecting approximately 10–15% long bone fractures, and is associated with pain, prolonged disability, repeated surgical interventions. Despite extensive research into the pathophysiological mechanisms healing, diagnostic approaches remain reliant on clinical findings radiographic evaluations, little innovation in tools to predict or diagnose non-union. The present review evaluates current understanding genetic biological basis pseudoarthrosis highlights future directions. Recent studies have highlighted potential specific molecules markers serve as predictors unsuccessful healing. Alterations mesenchymal stromal cell (MSC) function, including diminished osteogenic increased cellular senescence, are central pathogenesis. Molecular analyses reveal suppressed morphogenetic protein (BMP) signaling elevated levels its inhibitors, such Noggin Gremlin, which impair regeneration. Genetic uncovered polymorphisms BMP, matrix metalloproteinase (MMP), Wnt pathways, suggesting predisposition Additionally, differences between atrophic hypertrophic pseudoarthrosis, variations vascularity inflammatory responses, emphasize need for targeted management. Emerging biomarkers, circulating microRNAs (miRNAs), cytokine profiles, blood-derived MSCs, other (B7-1 PlGF-1), contribute early detection at-risk patients personalized therapeutic approaches. Advancing our underpinnings essential development innovative strategies.

Language: Английский

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LncRNA HCP5 : A Potential Biomarker for Diagnosing Gastric Cancer

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: June 18, 2021

It has been reported that long non-coding RNAs (lncRNAs) can be regarded as a biomarker and had particular clinical significance for early screening gastric cancer (GC) diagnosis. Therefore, this study aimed to investigate whether serum HCP5 could new diagnostic biomarker.Filtered out the from GEO database. The specificity of was verified by real-time fluorescence quantitative PCR (qRT-PCR), then stability room temperature storage repeated freeze-thaw experiments. Meanwhile, accuracy agarose gel electrophoresis (AGE) Sanger sequencing. Simultaneously, expression level detected qRT-PCR in 98 patients with primary cancer, 21 gastritis patients, 82 healthy donors, multiple types. Then, methodology analysis carried on. Moreover, receiver operating characteristic (ROC) used evaluate its efficiency.qRT-PCR method good repeatability detecting HCP5. remarkably higher than controls, it distinguish donors. Besides, increased dramatically MKN-45 MGC-803. FISH assay showed mainly distributed cytoplasm BGC-823 cells. When combined existing tumor markers, efficiency best, diagnosis carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), significantly improve sensitivity. compared levels thyroid (THCA), colorectal (CRC), breast (BRCA), most specific. high related differentiation, lymph node metastasis, nerve invasion. term after operation lower cancer.Serum potential non-invasive fluid biopsy, which unique value diagnosis, development, prognosis cancer.

Language: Английский

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Long non‐coding RNA AC018926.2 regulates palmitic acid exposure‐compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(8)

Published: Jan. 31, 2023

Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on development periodontitis and periodontal recovery from disease remains largely unknown. This study investigated cellular response ligament stem cells (PDLSCs) to elevated levels specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises osteogenic potential was also explored. It found that PDLSCs abundant led decreased cell differentiation. Given long non-coding RNAs (lncRNAs) play key role in adverse environmental stimuli, we screened lncRNAs were differentially expressed following using lncRNA microarray analysis, AC018926.2 identified most sensitive PA. Next, gain/loss-of-function studies illustrated an important regulator PA-mediated differentiation PDLSCs. Mechanistically, upregulated integrin α2 (ITGA2) expression therefore activated ITGA2/FAK/AKT signalling. Further functional revealed inactivation signalling silencing ITGA2 counteracted pro-osteogenic effect induced overexpression. Moreover, results bioinformatics analysis RNA immunoprecipitation assay suggested might transcriptionally regulate binding PARP1 protein. Our data suggest may serve therapeutic target management obese patients.

Language: Английский

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