MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes

Zhang, Yukun; Jia, Jie; Yang, Shuai; Liu, Xianzhe; Ye, Shunan; Tian, Hongtao

doi:10.1038/emm.2013.152

Cited by 103 publications

(78 citation statements)

References 28 publications

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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: 58%

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: 58%

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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“…The aberrant miRNA expression profiles have been demonstrated to be associated with OA [10,11], and miRNAs acted as important regulators in OA development, as well as participated in inflammatory response [12,13]. Previous studies have demonstrated that many miRNAs were involved in the regulation of OA, such as miR-320, miR-21, and miR-140 [14][15][16]. The miR-146a, as a negative regulator of leukocyte immune response, is involved in many other cell processes including cancer cell proliferation [17,18].…”

Section: Introductionmentioning

confidence: 99%

MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the Articular Chondrocytes

Sun

Song

et al. 2017

Cell Physiol Biochem

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Key WordsInflammatory injury • MicroRNA-146a • C-X-C chemokine receptor type 4 • PI3K/AKT • Wnt/β-catenin Abstract Background/Aims: Osteoarthritis (OA) as a degenerative disease is a major problem in ageing populations. To better understand the molecular mechanisms in the pathogenesis of OA, this study explored the role of microRNA (miR)-146a in the articular chondrocytes. Methods: The articular chondrocyte line ATDC5 was used to simulate inflammatory injury by LPS administration in vitro. Cell viability, apoptosis, mRNA expressions and productions of inflammatory factors were assessed, respectively. Mir-146a and Cxcr4 mRNA expressions were measured by qRT-PCR. Targeting effect of miR-146a on Cxcr4 3'UTR was assessed by luciferase activity analysis. Protein expression levels of CXCR4 and main factors in PI3K/AKT, Wnt/β-catenin signal pathways were measured by western blotting. Results: LPS exposure suppressed cell viability, prompted apoptosis of ATDC5 cells, and stimulated expression and release of inflammatory factors. MiR-146a was upregulated in LPS-induced cells. Overexpression of miR146a further aggravated LPS-induced inflammatory injury, while it was reduced after miR146a was knocked down. CXCR4 expression was negatively regulated by miR-146a. CXCR4 was a direct target of miR-146a and thus involved in regulatory effect of miR-146a on the injured chondrocytes, which was also related with phosphorylation levels of PI3K/AKT and expressions of Wnt/β-catenin signal factors. Conclusion: miR-146a promoted inflammatory response of articular chondrocytes via targeting CXCR4 and suppressing CXCR4 expression. Overexpression of CXCR4 could attenuate the inflammatory injury. Our findings provided novel evidence which might be useful for further studies exploring therapeutic approaches for OA via targeting miR-146a.

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“…Overexpression of miR-21 was reported to promote chondrocyte proliferation and matrix synthesis; interestingly, miR-21 was found to be reduced by food restriction [48] and to target GDF-5 in chondrocytes [115]. In an osteoarthritis model, the introduction of miR-21 stimulated the apoptosis of chondrocytes and inhibited the expression levels of autophagic complexes, including LC-3B, supporting our observation of increased autophagy in response to food restriction.…”

Section: Local Molecular Mechanisms In Malnutrition and Cu Growthsupporting

confidence: 71%

“…Moreover, in our model of nutritionally induced CU growth, we found that in the CU group, in contrast to the RES group, there was a rapid significant increase in the serum level of GDF-5 [112], suggesting an additional link between nutrition (mediated by the adipose tissue) and longitudinal growth. GDF-5 is also a target for nutritionally induced microRNAs (miRNAs, see below) [115] indicating an important role in the nutrition–growth complex. …”

Section: Systemic Factors In Malnutrition and Cu Growthmentioning

confidence: 99%

Effect of Nutrition on Statural Growth

Gat-Yablonski

Luca

2017

Horm Res Paediatr

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In children, proper growth and development are often regarded as a surrogate marker for good health. A complex system controls the initiation, rate, and cessation of growth, and thus gives a wonderful example of the interactions between genetics, epigenetics, and environmental factors (especially stress and nutrition). Malnutrition is considered a leading cause of growth attenuation in children. This review summarizes our current knowledge regarding the mechanisms linking nutrition and skeletal growth, including systemic factors, such as insulin, growth hormone, insulin-like growth factor-1, fibroblast growth factor-21, etc., and local mechanisms, including mTOR, miRNAs, and epigenetics. Studying the molecular mechanisms regulating skeletal growth may lead to the establishment of better nutritional and therapeutic regimens for more effective linear growth in children with malnutrition and growth abnormalities.

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MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes

Cited by 103 publications

References 28 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

MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the Articular Chondrocytes

Effect of Nutrition on Statural Growth

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