MicroRNA-16-5p Controls Development of Osteoarthritis by Targeting SMAD3 in Chondrocytes

Li, Lisong; Jia, Jie; Liu, Xianzhe; Yang, Shuhua; Ye, Shunan; Yang, Wen; Zhang, Yukun

doi:10.2174/1381612821666150909094712

Cited by 62 publications

(48 citation statements)

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“…Three independent experiments were performed in each assay. Several studies had demonstrated that miRNAs played a vital role in the regulation of the OA development, including miR-210 (21), miR-16 (22), miR-21 (23), and miR-142 (24). This study found the up-regulation of miR-4262 in TNF-α-treated chondrocytes.…”

Section: Discussionsupporting

confidence: 49%

miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

Sun

Li²,

Wei³

2017

Exp Ther Med

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Abstract. The present study aimed to investigate the effect and underlying mechanism of microRNA (miR)-4262 in the development of osteoarthritis (OA) in rats. Primary chondrocytes were separated from Sprague-Dawley rats and then treated with tumor necrosis factor-α (TNF-α). The level of miR-4262 was detected in TNF-α-treated chondrocytes, and then the miR-4262 or its target gene sirtuin type 1 (SIRT1) level was overexpressed, or knocked down. Furthermore, cell viability, cell apoptosis, cell autophagy and matrix synthesis, as well as the expressions of proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were detected. miR-4262 was significantly overexpressed in TNF-α-treated chondrocytes compared with untreated cells (P<0.05). TNF-α treatment or miR-4262 overexpression significantly decreased cell viability, autophagy-related proteins levels and matrix synthesis-related proteins levels, as well as increased the apoptotic rate in chondrocytes (P<0.05). Overexpression of SIRT1 significantly increased cell viability, autophagy-related proteins levels and matrix synthesis-related proteins levels, as well as decreased the apoptotic rate in TNF-α-treated chondrocytes (P<0.05). In addition, the effects of miR-4262 on cell viability, cell apoptosis, cell autophagy and matrix synthesis were inhibited by SIRT1 (P<0.05). Furthermore, upregulated miR-4262 remarkably increased the expressions of phosphorylated (p)-PI3K, p-AKT and p-mTOR (P<0.05) in TNF-α treated chondrocytes. The present study revealed that the upregulation of miR-4262 may promote the occurrence and development of OA in rats by regulating cell viability, cell apoptosis, cell autophagy, and matrix synthesis. Furthermore, these roles of miR-4262 may be associated with PI3K/AKT/mTOR signaling pathway.

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Section: Discussionsupporting

confidence: 49%

miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

Sun

Li²,

Wei³

2017

Exp Ther Med

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Section: Mirna Regulation Of Fibroblast Growth Factor 2 Transformmentioning

confidence: 99%

“…Also knee and hip AC of OA patients exhibit increased miR-16 expression compared to healthy AC [151,152]. SMAD3 has been determined as a direct target of miR-16, implicating this miRNA in the switch to catabolic TGF-β signaling [152]. Notably, FGF2 is a direct transcriptional target of miR-16 in human nasopharyngeal carcinoma cells [153], indicating additional repression of FGF2 signaling by this miRNA.…”

Section: Mirna Regulation Of Fibroblast Growth Factor 2 Transformmentioning

confidence: 99%

Onset and Progression of Human Osteoarthritis—Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?

Boehme,

Rolauffs

2018

IJMS

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Osteoarthritis (OA) is a degenerative whole joint disease, for which no preventative or therapeutic biological interventions are available. This is likely due to the fact that OA pathogenesis includes several signaling pathways, whose interactions remain unclear, especially at disease onset. Early OA is characterized by three key events: a rarely considered early phase of proliferation of cartilage-resident cells, in contrast to well-established increased synthesis, and degradation of extracellular matrix components and inflammation, associated with OA progression. We focused on the question, which of these key events are regulated by growth factors, inflammatory cytokines, and/or miRNA abundance. Collectively, we elucidated a specific sequence of the OA key events that are described best as a very early phase of proliferation of human articular cartilage (AC) cells and concomitant anabolic/catabolic effects that are accompanied by incipient pro-inflammatory effects. Many of the reviewed factors appeared able to induce one or two key events. Only one factor, fibroblast growth factor 2 (FGF2), is capable of concomitantly inducing all key events. Moreover, AC cell proliferation cannot be induced and, in fact, is suppressed by inflammatory signaling, suggesting that inflammatory signaling cannot be the sole inductor of all early OA key events, especially at disease onset.

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“…The cells were immunostained for collagen type II, as described in a previous study (18), prior to and after the experiments. Immunofluorescent images were gathered for each group using confocal laser scanning microscopy (LSM 710; Carl Zeiss AG, Oberkochen, Germany).…”

Section: Concentration Gradientmentioning

confidence: 99%

Effects of insulin-like growth factor 1 and basic fibroblast growth factor on the morphology and proliferation of chondrocytes embedded in Matrigel in a microfluidic platform

Fan

Jiang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. An integrated microfluidic device was utilized in the present study to investigate the morphology and proliferation of rabbit articular chondrocytes embedded in Matrigel in the presence of insulin-like growth factor 1 (IGF-1) and/or basic fibroblast growth factor (bFGF). The microfluidic device was composed of two parallel channels and a central perfusion-based three-dimensional cell culture module. The rabbit chondrocytes were cultured for 2 weeks at series of concentration gradients of IGF-1 and/or bFGF, which were generated through a diffusion process. At the end of the experiment, the morphology and quantity of cells were measured. Since high expression of collagen II is essential to the function of hyaline cartilage, immunofluorescent images of collagen II expression prior to and after the experiments were gathered for each group. The mean fluorescence intensity ratio (MIR) of collagen II in each group was calculated. The MIRs of collagen II in chondrocytes treated with IGF-1 ranged from 0.6-0.81, those in the cells treated with bFGF ranged from 0.47-0.52, and those in cells treated with a combination of IGF-1 and bFGF ranged from 0.63-0.83. Chondrocyte aggregations were observed in the group treated with 75-100 ng/ml IGF-1 (3.46-fold proliferation ratio). Similarly, a 3.83-fold proliferation ratio was identified in chondrocytes treated with 2.5-5.0 ng/ml bFGF. The group treated with 50-75 ng/ml IGF-1 and 2.5-5.0 ng/ml bFGF exhibited the optimum increase in proliferation (4.83-fold proliferation ratio). The microfluidic device used in the present study can be easily adapted to investigate other growth factors at any concentration gradient. In addition, parallel experiments can be performed simultaneously with a small quantity of cells, making it an attractive platform for the high-throughput screening of cell culture parameters. This platform will aid in the optimization of culture conditions for the in vitro expansion of chondrocytes while maintaining their in vivo morphology, which will improve autologous chondrocyte implantation capabilities for the treatment of cartilage injury.

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MicroRNA-16-5p Controls Development of Osteoarthritis by Targeting SMAD3 in Chondrocytes

Cited by 62 publications

References 0 publications

miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

miR-4262 regulates chondrocyte viability, apoptosis, autophagy by targeting SIRT1 and activating PI3K/AKT/mTOR signaling pathway in rats with osteoarthritis

Onset and Progression of Human Osteoarthritis—Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage?

Effects of insulin-like growth factor 1 and basic fibroblast growth factor on the morphology and proliferation of chondrocytes embedded in Matrigel in a microfluidic platform

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