PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway

Wang, H; Shan, Xinggen; Qiao, Yanguo

doi:10.1590/1414-431x20165988

Cited by 19 publications

(15 citation statements)

References 30 publications

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“…Normally, the MAPKs pathway consists of three signal cascades' pathway: c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) [ 19 ]. A large number of experiments suggested that the p38 signaling pathway plays a key role in the progress of considerable human diseases, especially for the development of OA [ 20 – 23 ]. Activation of the p38-MAPK signaling pathway may lead to the expression of proinflammatory cytokines, chemokines, MMPs, and signaling enzymes (COX-2) in human osteoarthritis chondrocytes [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway

Chen

Shou

Gong

et al. 2018

BioMed Research International

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It has been suggested that the activation of the p38 mitogen activated protein kinases (MAPKs) signaling pathway plays a significant role in the progression of OA by leading to the overexpression of proinflammatory cytokines, chemokines, and signaling enzymes in human osteoarthritis chondrocytes. However, most p38 MAPK inhibitors applied for OA have been thought to be limited due to their potential long-term toxicities. Geniposide (GE), an iridoid glycoside purified from the fruit of the herb, has been widely used in traditional medicine for the treatment of a variety of chronic inflammatory diseases. In this study, we evaluated the inhibition effect of geniposide on the inflammatory progression of the surgically induced osteoarthritis and whether the protective effect of geniposide on OA is related to the inhibition of the p38 MAPK signaling pathway. In vitro, geniposide attenuated the expression of inflammatory cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF-α), and nitric oxide (NO) production as well as matrix metalloproteinase- (MMP-) 13 in chondrocytes isolated from surgically induced rabbit osteoarthritis model. Additionally, geniposide markedly suppressed the expression of IL-1, TNF-α, NO, and MMP-13 in the synovial fluid from the rabbits with osteoarthritis. More importantly, our results clearly demonstrated that the inhibitory effect of geniposide on surgery-induced expression of inflammatory mediators in osteoarthritis was closely associated with the suppression of the p38 MAPK signaling pathways. Our study demonstrates that geniposide may have therapeutic potential to serve as an alternative agent for the p38 MAPK inhibition for the treatment of OA due to its inherent features of biological activities and low toxicity as a traditional Chinese medicine.

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Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway

Chen

Shou

Gong

et al. 2018

BioMed Research International

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“…Moreover, a previous study had validated that suppressing MAPK could inhibit the differentiation of bone marrow stromal cells in a way that could upregulate expression as well as phosphorylation of both ERK and JNK . Meanwhile, Wang et al demonstrated that the expressions of both JNK and ERK increased in bone marrow mesenchymal stem cells and that MDS with hematopoietic stem cells was associated with bone marrow diseases, indicating that both JNK and ERK could be upregulated in MDS . Subsequently, cyclin was collected and promoted rapidly with the information obtained from both CDK4 and CDK6 among patients diagnosed with MDS, indicating that cyclin D, CDK4, and CDK6 are being upregulated in MDS…”

Section: Discussionmentioning

confidence: 97%

Retracted: EBF1 gene promotes the proliferation and inhibits the apoptosis of bone marrow CD34+ cells in patients with myelodysplastic syndrome through negative regulation of mitogen‐activated protein kinase axis

Hou

Hao²,

Wang

et al. 2018

J of Cellular Biochemistry

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The transcription factor, early B cell factor 1 (EBF1), plays a vital role in the lineage specification involving early B cell development and the onset of myelodysplastic syndrome (MDS). Therefore, to investigate whether or not EBF1 affects MDS as well as the transcription factor's underlying mechanism, we used CD34+ hematopoietic stem cells in bone marrow from patients with MDS. The extracted cells were then transfected with a series of EBF1, short hairpin RNA against EBF1 (shEBF1), and SB203580 (a specific mitogen‐activated protein kinase [MAPK] axis inhibitor). The effects EBF1 gene and MAPK axis had on cell proliferation, apoptosis, and migration were determined by in vitro cell culturing. We made observations that involved EBF1 inhibiting the messenger RNA (mRNA) level of p38 MAPK, increasing the mRNA levels of extracellular‐signal–regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK), extracellular‐signal–regulated kinase 5 (ERK5), decreasing the protein expression of Bcl‐2–associated X protein (Bax), and finally elevating the protein levels of B cell lymphoma/leukemia‐2 (Bcl‐2), stem cell factor (SCF), erythropoietin receptor (EpoR), p‐ERK, p‐JNK, p‐ERK5, cyclin D, cyclin E, cyclin‐dependent kinase 2 (CDK2), and CDK6, implying that EBF1 may very well have an inhibitory role in the MAPK axis. Another discovery found that EBF1 had a positive effect on the promotion of bone marrow CD34+ cell proliferation as well as its migration, but inhibited the apoptosis of cells. The results we obtained from this study indicated that the EBF1 gene suppresses the activation of the MAPK axis, thereby promoting both the proliferation and migration of bone marrow CD34+ cells as well as inhibiting the associating apoptosis. The effects of the EBF1 gene are likely to present a new therapeutic target in preventing the progression of MDS.

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“…miR-455-3p overexpression downregulates the DNA methylation of cartilage development-related genes such as SOX6 and Smad3 . Both upregulation of SOX6 33 and Smad3 34 promotes chondrogenic differentiation of hMSCs.…”

Section: Discussionmentioning

confidence: 99%

MiR-455-3p inhibits the degenerate process of chondrogenic differentiation through modification of DNA methylation

et al. 2018

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The aim of this work was to determine whether miR-455-3p regulates DNA methylation during chondrogenic differentiation of hMSCs. The expression of miR-455-3p and de novo methyltransferase DNMT3A was assessed in micromass culture of hBMSCs, which induced chondrogenic differentiation in vitro, and in E16.5 mice in vivo. A luciferase reporter assay was used to confirm whether miR-455-3p directly targets DNMT3A by interaction with the 3′-UTR. Using an Illumina Infinium Methylation EPIC microarray, genome-wide DNA methylation of hBMSCs with or without overexpressed miR-455-3p was examined for 28 days during induced chondrogenic differentiation. Here, we showed that miR-455-3p was more expressed during the middle stage of hBMSC chondrogenic differentiation, and less expressed in the late stage. DNMT3A was less expressed in the middle stage and more expressed in the late stage, and was also more expressed in the palms of miR-455-3p deletion mice compared to those of wild-type mice. The luciferase reporter assay demonstrated that miR-455-3p directly targets DNMT3A 3′-UTR. miR-455-3p overexpression inhibits the degenerate process during chondrogenic differentiation, while deletion of miR-455-3p in mice accelerated cartilage degeneration. Genome-wide DNA methylation analysis showed miR-455-3p overexpression regulates DNA methylation of cartilage-specific genes. GO analysis revealed PI3K-Akt signaling pathway was most hypomethylated. Our data show that miR-455-3p can regulate hMSC chondrogenic differentiation by affecting DNA methylation. Overexpression of miR-455-3p and DNA methylation inhibitors can thus potentially be utilized to optimize chondrogenic differentiation.

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PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway

Cited by 19 publications

References 30 publications

Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway

Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway

Retracted: EBF1 gene promotes the proliferation and inhibits the apoptosis of bone marrow CD34+ cells in patients with myelodysplastic syndrome through negative regulation of mitogen‐activated protein kinase axis

MiR-455-3p inhibits the degenerate process of chondrogenic differentiation through modification of DNA methylation

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