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1.
Mol Med Rep ; 30(1)2024 Jul.
Article in English | MEDLINE | ID: mdl-38785157

ABSTRACT

Tributyltin chloride (TBTC) is known to have effects and mechanisms in various diseases; however, whether TBTC is detrimental to joints and causes osteoarthritis (OA), as well as its underlying mechanism, has not yet been fully elucidated. The present study explored the effects of TBTC on rat chondrocytes, as well as on mouse OA. The toxicity of TBTC toward rat chondrocytes was detected using a lactate dehydrogenase (LDH) leakage assay and cell viability was evaluated using the Cell Counting Kit­8 assay. The results showed that TBTC decreased the viability of rat chondrocytes and increased the LDH leakage rate in a concentration­dependent manner. Moreover, compared with in the control group, TBTC increased the expression levels of interleukin (IL)­1ß, IL­18, matrix metalloproteinase (MMP)­1, MMP­13, NLR family pyrin domain containing 3 (NLRP3), caspase­1, PYD and CARD domain containing, and gasdermin D in chondrocytes. Furthermore, knockdown of NLRP3 reversed the TBTC­induced increases in LDH leakage and NLRP3 inflammasome­associated protein levels. In vivo, TBTC exacerbated cartilage tissue damage in mice from the OA group, as evidenced by the attenuation of safranin O staining. In conclusion, TBTC may aggravate OA in mice by promoting chondrocyte damage and inducing pyroptosis through the activation of NLRP3 and caspase­1 signaling. The present study demonstrated that TBTC can cause significant damage to the articular cartilage; therefore, TBTC contamination should be strictly monitored.


Subject(s)
Chondrocytes , NLR Family, Pyrin Domain-Containing 3 Protein , Osteoarthritis , Pyroptosis , Trialkyltin Compounds , Animals , Chondrocytes/metabolism , Chondrocytes/drug effects , Chondrocytes/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Pyroptosis/drug effects , Mice , Rats , Osteoarthritis/metabolism , Osteoarthritis/pathology , Osteoarthritis/etiology , Male , Inflammation/metabolism , Inflammation/pathology , Inflammation/chemically induced , Caspase 1/metabolism , Inflammasomes/metabolism , Cell Survival/drug effects , Interleukin-1beta/metabolism , Signal Transduction/drug effects
2.
Histol Histopathol ; 38(6): 637-645, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35916204

ABSTRACT

BACKGROUND: Long noncoding RNA ubiquitin-conjugating enzyme E2 R2 antisense RNA 1 (UBE2R2-AS1) has been recently reported to participate in the progression of tumors, including glioma and liver cancer. However, the roles of UBE2R2-AS1 in prostate cancer (PC) remained poorly understood. METHODS: The expression of UBE2R2-AS1 was determined in tumor tissues and paired adjacent tissues from PC patients using quantitative reverse transcription PCR analysis. Correlation between UBE2R2-AS1 expression and clinicopathological parameters and overall survival were investigated by Chi-square test and Kaplan-Meier method analysis. The in vitro experiments, including CCK-8 assay, colony formation, flow cytometry and transwell assay were performed to investigate the functional role of UBE2R2-AS1 knockdown or overexpression on PC cell lines (PC-3 and DU145). Related protein expression levels were measured by western blot analysis. RESULTS: Our data showed that UBE2R2-AS1 expression was significantly upregulated in PC tissues compared with that in adjacent tissues. The high levels of UBE2R2-AS1 were associated with high Gleason score, advanced clinical T stage, lymph node metastasis and poor prognosis. Knockdown of UBE2R2-AS1 suppressed cell proliferation, migration and invasion, induced cell cycle G0/G1 arrest and apoptosis in PC cells, along with decreased expression of PCNA, CDK4, Cyclin D1, Bcl-2, N-cadherin and Vimentin, and increased E-cadherin expression. Overexpression of UBE12R2-AS1 obtained the opposite results in PC cells. CONCLUSIONS: Our findings suggest that UBE2R2-AS1 might be a potential diagnostic and/or therapeutic target in PC.


Subject(s)
Liver Neoplasms , Prostatic Neoplasms , RNA, Long Noncoding , Male , Humans , Prognosis , RNA, Long Noncoding/metabolism , Cell Proliferation/genetics , Cadherins/genetics , Prostatic Neoplasms/genetics , Cell Line, Tumor , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Ubiquitin-Conjugating Enzymes/genetics , Ubiquitin-Conjugating Enzymes/metabolism
3.
Exp Ther Med ; 22(6): 1478, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34765019

ABSTRACT

The present study aimed to investigate the expression and clinical significance of miR-519d-3p in patients with post-traumatic osteoarthritis (PTOA). The levels of miR-519d-3p in the synovium and synovial fluid (SF) of all subjects were detected by reverse transcription-quantitative polymerase chain reaction. The results of the present study demonstrated that the levels of miR-519d-3p in the synovium and SF of patients with PTOA were significantly lower, but that the VEGF content was significantly higher, compared with that of control group. Dual-luciferase reporter and Western blot assays demonstrated that VEGF was a target gene of miR-519d-3p. Furthermore, miR-519d-3p inhibitor-induced cell apoptosis, and cell cycle arrest could be partially reversed by silencing VEGF. Additionally, the level of miR-519d-3p in the synovium and SF of patients with PTOA was negatively correlated with the level of VEGF. ROC analysis demonstrated that miR-519d-3p levels in the synovium and SF could effectively differentiate patients with PTOA from healthy controls, with areas under the ROC curve of 0.928 and 0.896, respectively. In conclusion, reduction of miR-519d-3p in the synovium and SF resulted in the upregulation of VEGF in patients with PTOA, and miR-519d-3p may be a potential therapeutic target of PTOA.

4.
Clin Lab ; 63(11): 1819-1825, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-29226656

ABSTRACT

BACKGROUND: Increasing evidence has suggested the important role of miRNAs in the progression of osteoarthritis (OA). In the current study, we explored the role of miR-181-5p in the peripheral blood and bone tissues of OA patients for the first time. METHODS: The level of miR-181-5p was evaluated in the peripheral blood and cartilage of OA patients using real time PCR analysis. ROC analysis was performed to explore whether peripheral blood and cartilage miR-181-5p could screen OA patients from normal controls. Western blot assay and dual luciferase reporter assay were carried out to validate the possible target gene of miR-181-5p in SW1353 cells. RESULTS: For the first time, we confirmed that the expression of miR-181-5p was significantly reduced in the peripheral blood and cartilage of OA patients, suggesting that miR-181-5p may be involved in the process of cartilage injury in OA degradation. Furthermore, ROC analysis showed that both peripheral blood and cartilage miR181-5p could screen OA patients from healthy controls. Moreover, we found that overexpression of miR-181-5p significantly suppressed the expression of TNFα, while inhibition of miR-181-5p enhanced the level of TNFα. Bioinformatic predictions identified a conserved binding site in the 3'UTR of TNFα by miR-181-5p. In addition, dual luciferase reporter assay indicated that miR-181-5p markedly suppressed the relative luciferase activity of TNFα. These data indicated that TNFα was a target gene of miR-181-5p. CONCLUSIONS: In summary, reduced miR-181-5p expression in the peripheral blood and cartilage tissues may serve as a potential biomarker to screen OA patients from healthy controls mainly by targeting TNFα.


Subject(s)
MicroRNAs/blood , Osteoarthritis/blood , Adult , Aged , Bone and Bones/metabolism , Cartilage/metabolism , Case-Control Studies , Cell Line , Female , Humans , Male , Middle Aged , Osteoarthritis/diagnosis , Tumor Necrosis Factor-alpha/metabolism
5.
Ann Clin Lab Sci ; 46(3): 247-53, 2016 May.
Article in English | MEDLINE | ID: mdl-27312547

ABSTRACT

Osteoarthritis (OA) affects over 100 million individuals around the world. In this study, we mainly explore the functional role of miR-381a-3p in the regulation of OA. The expression of miR-381a-3p was studied in human articular cartilage and synovium of OA. Furthermore, the level of miR-381a-3p was analyzed in the OA rat model. MiR-381a-3p was overexpressed or inhibited with specific miR mimics or inhibitors. RT-PCR was applied to determine the levels of inflammatory factors such as TNFα, COX-2, iNOS, IL-6, and IL8. Bioinformatic predictions were applied to determine the possible target genes. Dual luciferase reporter assay was used to explore whether IκBα was the target gene of miR-381a-3p. The level of miR-381a-3p was significantly increased in the human articular cartilage and synovium of OA compared with normal control. Meanwhile, miR-381a-3p was enhanced in the OA rat model. Overexpression of miR-381a-3p significantly enhanced the levels of TNFα, COX-2, iNOS, IL-6 and IL8. IκBα was predicted as the target gene of miR-381a-3p. Dual luciferase reporter assay showed that miR-381a-3p could significantly decrease the luciferase activity of pmirGL-IκBα-3'UTR. In summary, enhanced miR-381a-3p expression contributed to the injury of OA mainly by inhibiting the expression of IκBα.


Subject(s)
MicroRNAs/metabolism , NF-KappaB Inhibitor alpha/genetics , Osteoarthritis/genetics , Animals , HEK293 Cells , Humans , Inflammation/pathology , MicroRNAs/genetics , NF-KappaB Inhibitor alpha/metabolism , NF-kappa B/metabolism , Rats, Sprague-Dawley , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism
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