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

Li, Fang; Yao, Jianhua; Hao, Qian; Duan, Zheping

doi:10.1042/bsr20191255

Cited by 30 publications

(21 citation statements)

References 34 publications

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“…In the researches of Soyocak [16] and others, miR-146a and miR-155 increased significantly in the progressive stage of OA, suggesting that they may be involved in the disease progression of OA. The researches by Li et al [17] have indicated that miR-103 can increase the level of chondrocyte apoptosis and promote the disease process of OA by inhibiting SPHK1 activity and PI3K/AKT pathway activation. miR-137, the main character of our study, was previously reported to be involved in the disease process of osteoporotic fracture.…”

Section: Introductionmentioning

confidence: 99%

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

Wang¹,

Fang²,

Ye³

et al. 2020

Bioscience Reports

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Purpose: To explore the regulatory mechanism of miR-137 and transcription factor 4 (TCF4) in the progression of osteoarthritis (OA). Patients and Methods: The expressions of miR-137 and TCF4 were detected in OA cartilage tissue, chondrocytes and OA rat cartilage tissue. miR-137 and TCF4 were up-regulated or down-regulated and transfected into chondrocytes and OA rat cartilage tissue. The gene expression, protein level, cell proliferation, apoptosis and inflammatory factors were detected, respectively. LPS and anterior cruciate ligament transection (ACLT) on the right knee were used to induce chondrocyte inflammation and establish rat OA model, respectively. Results: miR-137 was low expressed in cartilage tissue of OA group, while TCF4 expression and protein level were significantly higher, showing significant negative correlation. In LPS group, chondrocyte activity was significantly inhibited, cell apoptosis ability was significantly enhanced, and the levels of inflammatory factors TNF-α, IL-1β, IL-6 were significantly increased. However, the above results were significantly improved after the up-regulation of miR-137 or down-regulation of TCF4. Double luciferase report revealed that miR-137 and TCF4 had targeted relationship. LPS induced activation of AMPK/NF-κB pathway and higher level of apoptosis. AMPK/NF-κB pathway inhibitor C could inhibit activation of this pathway, and up-regulation of miR-137 or down-regulation of TCF4 could significantly weaken the regulation of LPS on the pathway and apoptosis. Analysis of OA rat model showed that over-expression of miR-137 could inhibit up-regulation of inflammatory factors and activation of AMPK/NF-κB pathway. Conclusion: miR-137 targets the inhibition of TCF4 to reverse the progression of OA through the AMPK/NF-κB signaling pathway.

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Section: Introductionmentioning

confidence: 99%

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

Wang¹,

Fang²,

Ye³

et al. 2020

Bioscience Reports

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“…Accumulating studies confirm that miRNAs figure prominently in OA progression. For example, miR-103 expression is significantly increased in the cartilage tissue of OA patients and rat models, and miR-103 can promote OA progression by down-regulating the PI3K/AKT pathway and reducing SPHK1 activity ( Li et al, 2019 ). MiR-146a expression is markedly raised in the OA model induced by IL-1β in vitro , and miR-146a can promote the pathogenesis of OA by targeting Smad4 to increase VEGF expression and inhibit the TGF-β signaling pathway ( Li et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

LncRNA MEG3 Protects Chondrocytes From IL-1β-Induced Inflammation via Regulating miR-9-5p/KLF4 Axis

et al. 2021

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BackgroundOsteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage damage, subchondral bone remodeling, osteophyte formation, and inflammatory changes. This work aims to investigate the protective role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) against the apoptosis of chondrocytes.MethodsChondrocyte cell lines, CHON-001, and ATDC5 were treated with different doses of interleukin-1β (IL-1β) to mimic the inflammatory response during OA pathogenesis. Quantitative real-time polymerase chain reaction was performed to measure MEG3, miR-9-5p, and Krüppel-like factor 4 (KLF4) mRNA expression levels. MEG3 and KLF4 overexpression plasmids, MEG3 shRNA, miR-9-5p mimics, and miR-9-5p inhibitors were transfected into the cells. Cell counting kit-8, wound healing assay, and flow cytometry were conducted to determine cell viability, migration, and apoptotic rate. Dual-luciferase reporter assay was adopted to verify the targeting relationships among MEG3, miR-9-5p, and KLF4. Western blot was used to detect KLF4 protein expression. Enzyme-linked immunosorbent assay was employed to measure the levels of inflammatory factors.ResultsMEG3 expression in chondrocytes was down-regulated by the stimulation of IL-1β, and MEG3 negatively regulated miR-9-5p expression but positively regulated KLF4 expression. MEG3 overexpression strengthened the viability and migration of CHON-001 and ATDC5 cells but restrained the apoptosis and inflammatory response, while MEG3 knockdown had opposite effects. miR-9-5p inhibition or KLF4 overexpression could counteract the effects of MEG3 knockdown on chondrocytes. Besides that, MEG3 was proved to be a molecular sponge for miR-9-5p, and KLF4 was verified as the target of miR-9-5p.ConclusionMEG3 can promote chondrocyte proliferation and migration and inhibit apoptosis and inflammation by sponging miR-9-5p to induce KLF4 expression, which provides a promising therapy target for OA treatment.

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“…In OA chondrocytes it has been observed a number of up-regulated miRNAs. In particular, miR-9 down-regulates monocyte chemoattractant protein-induced protein 1 expression, promoting IL-6 expression and chondrocyte apoptosis [ 201 ]; miR-103 induces cell apoptosis and suppresses cell proliferation down-regulating PI3K/AKT pathway by blocking sphingosine kinase 1 expression [ 202 ]; miR-34a promotes apoptosis by directly regulating the silent information regulator 1 (SIRT1)/p53 signaling pathway [ 203 ] or through the delta-like protein 1 via PI3K/AKT pathway [ 204 ]. SIRT1, in particular, is a deacetylase playing a crucial role in the prevention of apoptosis, enhancing acetylated p53 and Bax and down-regulating Bcl-2.…”

Section: Apoptosis and Cartilage Calcificationmentioning

confidence: 99%

Apoptosis in the Extraosseous Calcification Process

Boraldi

Lofaro

Quaglino

2021

Cells

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Extraosseous calcification is a pathologic mineralization process occurring in soft connective tissues (e.g., skin, vessels, tendons, and cartilage). It can take place on a genetic basis or as a consequence of acquired chronic diseases. In this last case, the etiology is multifactorial, including both extra- and intracellular mechanisms, such as the formation of membrane vesicles (e.g., matrix vesicles and apoptotic bodies), mitochondrial alterations, and oxidative stress. This review is an overview of extraosseous calcification mechanisms focusing on the relationships between apoptosis and mineralization in cartilage and vascular tissues, as these are the two tissues mostly affected by a number of age-related diseases having a progressively increased impact in Western Countries.

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

Cited by 30 publications

References 34 publications

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

LncRNA MEG3 Protects Chondrocytes From IL-1β-Induced Inflammation via Regulating miR-9-5p/KLF4 Axis

Apoptosis in the Extraosseous Calcification Process

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