JOURNAL OF PHARMACOLOGICAL SCIENCES
·
2024
·
IF 3
Zhihang Zhang,Yalan Luo,Xijing Zhuang,Haifeng Gao,Qi Yang,Hailong Chen
Acute lung injury (ALI) is closely related to high mortality in severe acute pancreatitis (SAP). This study unveils the therapeutic effect and mechanism of miR-217-5p on SAP-associated ALI. The miR-217-5p RNA expression was significantly up-regulated in lipopolysaccharide (LPS)-stimulated primary rat alveolar epithelial type II cells (AEC II) and sodium taurocholate-treated pancreas and lung in SAP rats. miR-217 inhibition protected AEC II from LPS-induced damage by inhibiting apoptosis and reducing the TNF-α, IL-6, and ROS levels. miR-217 inhibition suppressed apoptosis and alleviated mitochondrial damage through mitochondria-mediated apoptotic pathway in vitro . Sirt1 is a direct target of miR-217-5p. Dual-luciferase reporter assay confirmed the binding of miR-217-5p to Sirt1 mRNA 3′-UTR. The rescue experiment identified that the anti-apoptotic, anti-inflammatory, and anti-oxidative effects of miR-217 inhibition were mediated by Sirt1 in vitro . Emodin (EMO) protected AEC II from LPS-induced damage and alleviated pancreatic and lung tissue injuries. EMO exerted similar effects as miR-217 inhibition in vitro and in vivo . The effects of EMO were abolished by miR-217 overexpression. In conclusion, miR-217-5p inhibition exerts protective effects on SAP-ALI in vitro and in vivo by repressing apoptosis, inflammation, and oxidative stress through Sirt1 activation. EMO protects against lung injuries in SAP-associated ALI rats through miR-217-5p/Sirt1 axis.
研究领域:
药理学
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分子生物学
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病理生理学
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内科学
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产品关联
DOI
PubMed
高影响因子
DRUG AND CHEMICAL TOXICOLOGY
·
2025
·
IF 1.9
Aicun Tang,Luying Wei,Jiayi Gao,Zheng Zhang,Bingyu Xia,Xin Li,Qiuyu Lu
To analyze tadehaginoside (TA) for its effect on liver fibrosis and the associated mechanism. Mice with CCl4-mediated liver fibrosis were administered TA treatment for 6 weeks. Histopathological alterations in liver tissues were evaluated, and serum markers of hepatic injury, as well as the hepatic profibrotic gene and protein levels were detected. Transforming growth factor-β1 (TGF-β1) was adopted for inducing LX-2 cells. Following a 24-h TA intervention, we assessed pro-fibrotic gene and protein activation, proliferation and levels of TGF-β1-activated LX-2 cells. miR-155 and FOXO3 expressions were quantified in mice liver tissues and cells. The targeting relation of miR-155 with FOXO3 was verified. After regulating miR-155 and FOXO3 expression, the function of TA in cell activation, proliferation, and collagen accumulation was evaluated. The results indicated that TA treatment markedly alleviated CCl4-mediated mouse liver injury, inhibited collagen fiber deposition, and downregulated the hepatic pro-fibrotic gene and protein levels. Additionally, TA treatment suppressed TGF-β1-induced cell activation and proliferation, thus significantly reducing pro-fibrotic marker levels within cells. Furthermore, treatment with TA down-regulated miR-155 and up-regulated FOXO3 within CCl4-induced liver tissues as well as TGF-β1-induced cells. However, miR-155 overexpression or FOXO3 silencing partially mitigated the inhibition of TA against TGF-β1-mediated activation, proliferation, and fibrosis in cells. In conclusion, TA inhibits the activation of hepatic stellate cell (HSC) via miR-155/FOXO3 axis, thereby exerting its anti-hepatic fibrosis effect.
研究领域:
药理学
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分子生物学
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肝脏病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Yiren Xiong,Jiayi He,Shanshan He,Zuqing Hu,Di Ouyang,Renyi Liu,Zhenjie Gao,Weiguang Zhang,Zhujun Kang,Shuyi Lan,Yang Wang,Fatoumata Diallo,Dalin Hu
Lead is a ubiquitous environmental chemical with various toxic damage to human body. This investigation aimed to explore the intervention effect of human umbilical cord mesenchymal stem cells derived exosomes (HUC-MSC-exo) on the neurotoxicity of lead and the relevant mechanism. Differential gradient ultracentrifugation was adopted to isolate HUC-MSC-exo. Nanoparticle tracking assay (NTA), Transmission electron microscope (TEM) technology and exosomal specific biomarkers CD9, CD63 and CD81 were adopted for exosomal characterization. Human neuroblastoma cell (SH-SY5Y) was used as the recipient cell. Confocal laser scanning microscope analysis was conducted to confirm the intake of HUC-MSC-exo by SH-SY5Y cells. Cell migration ability, apoptosis, IL-6, IL-1β and TNF-α were analyzed. The role of miR-26a-5p/PTEN axis was assessed. The result showed that the exposure of SH-SY5Y cells to lead activated the miR-26a-5p/PTEN pathway by down-regulating miR-26a-5p and up-regulating PTEN expression, which was related to the significantly decreased cell migration and increased apoptosis, as well as significantly enhanced levels of inflammatory cytokine as compared with the control. While HUC-MSC-exo could significantly alleviate the cytotoxicity, apoptosis and inflammatory effects induced by lead on SH-SY5Y cells via partially restoring miR-26a-5p/PTEN pathway. Herein, we conclude that HUC-MSC-exo can alleviate lead-induced toxic effects on SH-SY5Y cells partially through miR-26a-5p/PTEN pathway.
研究领域:
毒理学
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干细胞研究
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Guoqiang Xu,Xiaona Song,Xiaotang Wang,Rui Xue,Xiaoru Yan,Litao Qin,Xiaoqi Chang,Jiping Gao,Zhaoyang Chen,Guohua Song
Purpose Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.Methods We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.Results The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.Conclusion Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PSYCHOPHARMACOLOGY
·
2018
·
IF 4.738
Li-Tao Yi,Rong-Hao Mu,Shu-Qi Dong,Shuang-Shuang Wang,Cheng-Fu Li,Di Geng,Qing Liu
Our previous study demonstrated that gypenosides produced antidepressant-like effects in mice exposed to chronic mild stress in a brain-derived neurotrophic factor-dependent manner. However, whether other mechanisms are involved in the antidepressant-like effects of gypenosides is not clear. miR-124 is one of the most abundant microRNAs in the hippocampus, and its dysregulation is related to the pathophysiology of depression. The glucocorticoid receptor is dysfunctional in depression, and it is a direct target of miR-124. Therefore, the present study used corticosterone-induced mice as a model to evaluate the role of miR-124 on the antidepressant-like effects of gypenosides. miR-124 agomir was intracerebrally injected prior to administration of gypenosides and corticosterone injection. Sucrose preference and forced swimming tests were performed 21 days later. Proteins related to glucocorticoid receptors and brain-derived neurotrophic factor-tyrosine receptor kinase B signaling in the hippocampus were evaluated. Our results demonstrated that gypenosides reversed the chronic corticosterone injection-induced decreased sucrose preference and increased immobility time. In contrast, this effect was antagonized by miR-124 injection. In addition, gypenosides increased glucocorticoid receptor and tyrosine receptor kinase B expression in the hippocampus, which activated brain-derived neurotrophic factor signaling. miR-124 also blocked these effects. In conclusion, this study demonstrated that a reduction in miR-124 was required for the antidepressant-like effects of gypenosides induced by chronic corticosterone injection in mice.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Shaojun Liang,Yan Duan,Zhen Xing,Haobo Han,Aijun Zhang,Li Li,Yan Yang,Quanshun Li
Chondroitin sulfate was chemically conjugated to PEI25K through Michael addition to construct a non-viral gene carrier CS-PEI, and then the carrier was employed in miR-34a delivery to achieve the inhibition of cell proliferation and migration, using prostate tumor cell PC-3 as a model. The nanoparticle from CS-PEI and miR-34a at a mass ratio of 10 was prepared with particle size and zeta potential of 170.7 nm and +42.2 mV, respectively. Flow cytometry and fluorescence microscopy revealed that CS-PEI could efficiently induce the cellular uptake of miR-34a in a CD44-mediated endocytosis manner. Through CS-PEI-mediated miR-34a transfection, obvious cell apoptosis was observed with early apoptotic cells of 47.49%, and meanwhile the activation of caspase-3, -8 and -9, and decreased expression level of Bcl-2 were detected. Moreover, wound healing assay showed that CS-PEI/miR-34a transfection could inhibit the cell migration. Overall, CS-PEI is potentially employed as a promising tumor-targeting system for miR-34a delivery in tumor gene therapy.
研究领域:
药学
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分子生物学
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癌症研究
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基因治疗
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产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2016
·Vol. 41
·期 8
·2110-2118
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IF 2.472
Zhu Mingming,Li Bingfei,Ma Xiao,Huang Cong,Wu Rui,Zhu Weiwei,Li Xiaoting,Liang Zhaofeng,Deng Feifei,Zhu Jianyun,Xie Wei,Yang Xue,Jiang Ye,Wang Shijia,Wu Jieshu,Geng Shanshan,Xie Chunfeng,Zhong Caiyun,Liu Haiyan
Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.
研究领域:
神经科学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BMC Urology
·
2023
·Vol. 23
·期 1
·1-11
·
IF 2
Pan Gaojian,Jiang Bo,Yi Zhongquan,Yin Jiuhu,Liu Yadong
Bladder cancer stem cells (BCSCs) are considered as the root cause of BC initiation and recurrence, and exosomes derived from BCSCs (CSCs-exo) are the vital tool for establishing a stable tumor microenvironment. miR-105-5p has been revealed to promote tumor growth in a variety of cancers, but the effects on BC are still not included.Characteristics of CSCs-exo were examined by transmission electron microscope and nanoparticle tracking analysis. PKH67 dye was used to observe the cellular uptake of exosomes. Cell viability, migration and invasion were detected by CCK-8, wound healing and transwell invasion assays, respectively. The interaction between miR-105-5p and GPR12 was verified by luciferase activity assay. Xenografts were induced in the nude mice, and H&E staining method was applied to analyze the histological changes of xenografts. CSCs-exo efficiently promoted BC cell viability, migration and invasion. miR-105-5p was highly expressed in CSCs and CSCs-exo treatment significantly upregulated the expression of miR-105-5p in BC cells.GPR12 was subsequently verified to be the target gene of miR-105-5p, and overexpression of GPR12 abrogated the effects of miR-105-5p on BC cell growth and metastasis. Reversely, the anti-tumor function of miR-105-5p antagomir was observed in the xenograft mice.CSCs aggravated the malignancy of BC partly through transmitting exosomal miR-105-5p to BC cells to inhibit the expression of GPR12, which developed a novel aspect for CSC-targeted therapies.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Leiliang He,Lihua Ding,Songcheng Yu,Fei Yu,Yongmei Tian,Xinsheng Xie,Lingbo Qu,Lie Liu,Yongjun Wu
The establishment of a highly sensitive and efficient platform for detecting circulating miRNA in serum is important for disease diagnosis and prognosis. To this end, a self-assembled horseradish peroxidase (HRP)-based polymer (poly-HRP) dual signal amplification strategy, via skillful combination of functionalized magnetic nanoparticles as the capture nanoprobes and the poly-HRP as signal amplification probes, has been developed for highl-sensitive and accurate detection of circulating miR-142-3p in human serum. Just by mixing building blocks together at one time, the poly-HRP used for dual signal amplification can be engineered by only one-step assembly. As the poly-HRP can be directly prepared ahead, avoiding chain amplification reaction in the detection process, the assay can be rapidly accomplished in about one hour. The measured limit-of-detection (LOD) is down to 100 fM. Standard miR-142-3p spiked in human serum is measured with ideal recovery rates ranging from 97.46% to 115.90%. More importantly, this method was validated to be applicable to direct detection of miR-142-3p in serums, and the results suggested that the miR-142-3p levels of serum samples obtained from T-cell acute lymphoblastic leukemia children (n = 25) are significantly higher than those from healthy control groups (n = 25) ( P < 0.01). To conclude, the ingenious combination of functionalized magnetic nanoparticles and the poly-HRP presented in this work brings forth a rapid, convenient, yet simple, sensitive, and specific biosensing method that can potentially be applied for clinical diagnosis.
研究领域:
生物化学
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分子生物学
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临床诊断
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产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2025
·
IF 3.6
Mengdie Liu,Jian Wang,Yan Lv,Qiang Sun,Bin Guo
Facial nerve injury (FNI) causes devastating sequelae, including impaired eyelid closure, dysphagia, and permanent facial asymmetry, leading to long-term functional deficits and profound psychosocial impacts that pose significant rehabilitation challenges. To address this, neural regenerative scaffolds represent a promising therapeutic alternative. This study engineered poly(L-lactic acid) (PLLA) electrospun membranes with parallel topographical cues (Align) and functionalized miR-451a-incorporated scaffolds (miR-451a mimics@PLLA) via electrostatic spinning, aiming to decipher how topographical cues steer neurogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and their crosstalk with microRNA regulation. We demonstrate that parallel topography substantially upregulates neurulation-associated biomarkers (Tuj-1, S100, NeuroD1, Map2, and Nestin) in BMSCs, while miR-451a synergistically enhances this differentiation efficacy. The developed miR-451a mimics@PLLA scaffold effectively promotes BMSC neurogenic commitment and functional nerve regeneration, offering a novel biomimetic strategy to overcome FNI complications. This work pioneers synergistic integration of topological engineering and miRNA delivery for next-generation neural repair scaffolds.
研究领域:
神经科学
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生物材料
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组织工程
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干细胞研究
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RNA生物学
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产品关联
DOI
PubMed
高影响因子
RNA Biology
·
2021
·
IF 4.652
Yan Wang,Yujie Guo,Xiaolei Zhang,Hui Zhao,Bingbing Zhang,Yi Wu,Jingyu Zhang
Specific miRNA in immune thrombocytopenia (ITP) was screened to explore its intervention effects and mechanisms in ITP. MTT assay and CFSE staining were used to detect the effects of gradient concentrations of thrombopoietin (TPO) on cell proliferation. Expressions of differentially expressed miRNAs were analysed via qRT-PCR in TPO-induced megakaryocytes and ITP plasma. Effects of miR-557 on cell physiological functions were examined by MTT and flow cytometry. Expressions of miR-557, apoptosis-associated genes and Akt/ERK pathways were detected by qRT-PCR and Western blot as needed. Multinucleation of TPO-induced megakaryocytes was determined by megakaryocyte colonies. The toe skin and intestinal bleeding of the ITP rat model were observed and evaluated. Effects of miR-557 on the numbers of platelets, megakaryocytes, and peripheral blood platelets and the expressions of CD4+ T cells, Treg cells, TGF-β, IL-6 and miR-557 in the ITP rats were detected by Giemsa staining, flow cytometry, ELISA and qRT-PCR. MiR-557 was identified as an specific miRNA associated with both ITP and TPO treatment. MiR-557 inhibitor enhanced the physiological functions of TPO-induced megakaryocytes, while miR-557 mimic had the opposite effect. At the molecular level, the expressions of miR-557, cleaved Caspase-3 and Bax were further silenced by inhibitor, on the contrary, the expressions of bcl-2, p-Akt and p-ERK were upregulated. Animal experiments showed that, miR-557 inhibitor increased the numbers of platelets and megakaryocytes, and improved the symptoms of ITP model rats. Our results indicated that miR-557 inhibitor improved ITP by regulating apoptosis-related genes and cellular immunity and activating the Akt/ERK pathway.
研究领域:
血液学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
MOLECULAR BIOLOGY REPORTS
·
2024
·Vol. 51
·期 1
·1-15
·
IF 2.6
Wumiti Taxi,Wang Lining,Xu Bin,Ma Yong,Zhu Yihua,Zuo Xinchen,Qian Weiqing,Chu Xudong,Sun Haitao
Background Promoting the balance between bone formation and bone resorption is the main therapeutic goal for postmenopausal osteoporosis (PMOP), and bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation plays an important regulatory role in this process. Recently, several long non-coding RNAs (lncRNAs) have been reported to play an important regulatory role in the occurrence and development of OP and participates in a variety of physiological and pathological processes. However, the role of lncRNA tissue inhibitor of metalloproteinases 3 (lncTIMP3) remains to be investigated. Methods The characteristics of BMSCs isolated from the PMOP rat model were verified by flow cytometry assay, alkaline phosphatase (ALP), alizarin red and Oil Red O staining assays. Micro-CT and HE staining assays were performed to examine histological changes of the vertebral trabeculae of the rats. RT-qPCR and western blotting assays were carried out to measure the RNA and protein expression levels. The subcellular location of lncTIMP3 was analyzed by FISH assay. The targeting relationships were verified by luciferase reporter assay and RNA pull-down assay. Results The trabecular spacing was increased in the PMOP rats, while ALP activity and the expression levels of Runx2, Col1a1 and Ocn were all markedly decreased. Among the RNA sequencing results of the clinical samples, lncTIMP3 was the most downregulated differentially expressed lncRNA, also its level was significantly reduced in the OVX rats. Knockdown of lncTIMP3 inhibited osteogenesis of BMSCs, whereas overexpression of lncTIMP3 exhibited the reverse results. Subsequently, lncTIMP3 was confirmed to be located in the cytoplasm of BMSCs, implying its potential as a competing endogenous RNA for miRNAs. Finally, the negative targeting correlations of miR-214 between lncTIMP3 and Smad4 were elucidated in vitro. Conclusion lncTIMP3 may delay the progress of PMOP by promoting the activity of BMSC, the level of osteogenic differentiation marker gene and the formation of calcium nodules by acting on the miR-214/Smad4 axis. This finding may offer valuable insights into the possible management of PMOP.
研究领域:
骨生物学
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干细胞生物学
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分子生物学
·
非编码RNA
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骨质疏松症
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）