microRNA-186 inhibition of PI3K-AKT pathway via SPP1 inhibits chondrocyte apoptosis in mice with osteoarthritis

2018 ◽  
Vol 234 (5) ◽  
pp. 6042-6053 ◽  
Author(s):  
Zeng Lin ◽  
Xin-Yi Tian ◽  
Xi-Xi Huang ◽  
Ling-Li He ◽  
Feng Xu
Keyword(s):  
Akt Pathway ◽  
Chondrocyte Apoptosis

scholarly journals MiR‐155 promotes interleukin‐1β‐induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1‐mediated PI3K/Akt pathway

2020 ◽  
Vol 24 (15) ◽  
pp. 8441-8451
Author(s):  
Zhiyong Fan ◽  
Yinghui Liu ◽  
Zhengliang Shi ◽  
Kai Deng ◽  
Hua Zhang ◽  
...  
Keyword(s):  
Interleukin 1Β ◽  
Akt Pathway ◽  
Chondrocyte Apoptosis ◽  
Catabolic Activity

scholarly journals miRNA-103 promotes chondrocyte apoptosis by down-regulation of Sphingosine kinase-1 and ameliorates PI3K/AKT pathway in osteoarthritis

2019 ◽  
Vol 39 (10) ◽  
Author(s):  
Fang Li ◽  
Jianhua Yao ◽  
Qingqing Hao ◽  
Zheping Duan
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Sphingosine Kinase ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Chondrocyte Apoptosis ◽  
Sphingosine Kinase 1 ◽  
Down Regulation ◽  
Induced Apoptosis

Abstract Objectives: The aim of the present study was to determine the effects of miRNA-103 on chondrocyte apoptosis and molecular mechanisms in osteoarthritis (OA) progression. Methods: The cell proliferation, apoptosis, and recovery ability were measured by cell counting kit-8 (CCK-8), flow cytometry, and wound healing assays. The interaction of miRNA-103 and Sphingosine kinase-1 (SPHK1) were determined by using luciferase reporter assay. The expression of mRNA and proteins were measured by qRT-PCR and Western blot. OA rat model was established by surgery stimulation. Results: miRNA-103 expression was significantly increased in the cartilage of OA patients and surgery-induced OA rat models. miRNA-103 transfection into primary rat chondrocytes reduced SPHK1 expression, induced apoptosis, inhibited cell proliferation, and impeded scratch assay wound closure. Moreover, expression of total AKT, and p-AKT were significantly reduced in miRNA-103-overexpressing chondrocytes while SPHK1 up-regulation increased the expression of phosphatidylinsitol-3-kinase (PI3K) and p-AKT, and reversed the proliferation suppression induced by the miRNA-103 mimic. Conclusions: Our studies suggest that miRNA-103 contributes to chondrocyte apoptosis, promoting OA progression by down-regulation of PI3K/AKT pathway through the reduction in SPHK1 activity.

scholarly journals MiR-34a Enhances Chondrocyte Apoptosis, Senescence and Facilitates Development of Osteoarthritis by Targeting DLL1 and Regulating PI3K/AKT Pathway

2018 ◽  
Vol 48 (3) ◽  
pp. 1304-1316 ◽  
Author(s):  
Wei Zhang ◽  
Peichun Hsu ◽  
Biao  Zhong ◽  
Shang Guo ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Cell Death ◽  
Target Genes ◽  
Cartilage Degeneration ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Chondrocyte Apoptosis ◽  
Articular Chondrocyte ◽  
Reporter System ◽  
Chondrocyte Death

Background/Aims: Osteoarthritis (OA) is the prevalent degenerative disease caused by various factors. MicroRNAs are important regulators in the inflammation and immune response. The aim of this study was to investigate the effect of microRNA-34a (MiR-34a) on the death of chondrocytes, senescence, as well as its role in OA progression. Methods: A series of experiments involving CCK-8, flow cytometry, β-galactosidase staining and wound healing assays were conducted to determine the cellular capabilities of proliferation, cell apoptosis, senescence and the ability of cells to recover from injury, respectively. Binding sites between miR-34a and delta-like protein 1 (DLL1) were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT-PCR and immunoblot, respectively. OA model was generated via surgery. Results: We found that miR-34a expression was increased in the cartilage of OA patients. In rat chondrocytes and chondrosarcoma cells, miR-34a transfections noticeably inhibited the expression of DLL1, triggered cell death and senescence, suppressed proliferation, and prevented scratch assay wound closure. However, transfection of a miR-34a inhibitor displayed adverse effects. Additionally, secretion and expression of factors associated with cartilage degeneration were altered via miR-34a. Moreover, miR-34a directly inhibits DLL1 mRNA. Furthermore, concentrations of DLL1, total PI3K, and p-AKT declined in chondrocytes that overexpress miR-34a. DLL1 overexpression elevated PI3K and p-AKT levels, and eliminated cell death triggered by a miR-34a mimic. In vivo, miR-34a remarkably inhibited miR-34a up-regulation, while enhanced the level of DLL1 expression. In the knee joints of surgery-induced OA rats, articular chondrocyte death and loss of cartilage were attenuated via miR-34a antagomir injection. Conclusions: These findings indicate that miR-34a contributes to chondrocyte death, causing OA progression through DLL1 and modulation of the PI3K/AKT pathway.

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