Role of P2×7 receptor in the differentiation of bone marrow stromal cells into osteoblasts and adipocytes

Li, Wenkai; Li, Guizhen; Zhang, Yingchi; Wei, Sheng; Song, Min-Ji; Wang, Wei; Yuan, Xuefeng; Wu, Hua; Yong, Yang

doi:10.1016/j.yexcr.2015.10.011

Cited by 37 publications

(41 citation statements)

References 53 publications

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“…The MAPK signaling pathway, which is a group of serine/threonine protein kinases involved in the cellular signal transduction [60], which regulated many cellular functions, affects a large number of human diseases. Previous studies have demonstrated the effect of MAPK signals on tumor metastasis [61,62], osteogenesis [63,64], osteoarthritis [65,66], or certain inflammatory diseases [67]. For example, it can regulate the proliferation and differentiation of brain cells [68].…”

Section: Discussionmentioning

confidence: 99%

Plasma Exosome-derived MicroRNAs as Novel Biomarkers of Traumatic Brain Injury in Rats

Wang

Zhang

et al. 2020

Int. J. Med. Sci.

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Traumatic brain injury (TBI) is a widespread central nervous system (CNS) condition and a leading cause of death, disability, and long-term disability including seizures and emotional and behavioral issues. To date, applicable diagnostic biomarkers have not been elucidated. MicroRNAs (miRNAs) are enriched and stable in exosomes in plasma. Therefore, we speculated that miRNAs in plasma exosomes might serve as novel biomarkers for TBI diagnosis and are also involved in the pathogenesis of TBI. In this study, we first isolated exosomes from peripheral blood plasma in rats with TBI and then investigated the alterations in miRNA expression in exosomes by high-throughput RNA sequencing. As a result, we identified 50 significantly differentially expressed miRNAs, including 31 upregulated and 19 downregulated miRNAs. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the most highly correlated pathways that were identified were the MAPK signaling pathway, regulation of actin cytoskeleton, Rap1 signaling pathway and Ras signaling pathway. This study provides novel perspectives on miRNAs in peripheral blood plasma exosomes, which not only could be used as biomarkers of TBI diagnosis but could also be manipulated as therapeutic targets of TBI.

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Section: Discussionmentioning

confidence: 99%

Plasma Exosome-derived MicroRNAs as Novel Biomarkers of Traumatic Brain Injury in Rats

Wang

Zhang

et al. 2020

Int. J. Med. Sci.

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“…ATP decreases adipogenesis and reduces lipid droplets formation through the P2Y2 receptor activation and antagonizing the P2Y4 receptor (Zippel et al, ). Accordingly, the activation of the P2X7 receptor by BzATP resulted in a decrease in the expression of adipogenic marker genes and the number of adipocytes generated by bone marrow MSCs, and this effect was shown to be attenuated by P2X7‐specific siRNA (W. Li et al, ). In addition, the application of apyrase (NTPDase) enhanced lipid droplets formation, thus confirming the inhibitory effect of ATP.…”

Section: Differentiation Of Mscsmentioning

confidence: 99%

How to influence the mesenchymal stem cells fate? Emerging role of ectoenzymes metabolizing nucleotides

Roszek

Wujak

2018

Journal Cellular Physiology

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Extracellular purines, principally adenosine triphosphate and adenosine, are among the oldest evolutionary and widespread chemical messengers. The integrative view of purinergic signaling as a multistage coordinated cascade involves the participation of nucleotides/nucleosides, their receptors, enzymes metabolizing extracellular nucleosides and nucleotides as well as several membrane transporters taking part in the release and/or uptake of these molecules. In view of the emerging data, it is evident and widely accepted that an extensive network of diverse enzymatic activities exists in the extracellular space. The enzymes regulate the availability of nucleotide and adenosine receptor agonists, and consequently, the course of signaling events. The current data indicate that mesenchymal stem cells (MSCs) and cells induced to differentiate exhibit different sensitivity to purinergic ligands as well as a distinct activity and expression profiles of ectonucleotidases than mature cells. In the proposed review, we postulate for a critical role of these enzymatic players which, by orchestrating a fine-tune regulation of nucleotides concentrations, are integrally involved in modulation and diversification of purinergic signals. This specific hallmark of the MSC purinome should be linked with cell-specific biological potential and capacity for tissue regeneration. We anticipate this publication to be a starting point for scientific discussion and novel approach to the in vitro and in vivo regulation of the MSC properties.

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“…Furthermore, P2X7R serves an essential role in the regulation of MAPK pathways during physiological and pathological processes, such as sympathoexcitatory response in myocardial infarction (35) and the differentiation of bone marrow stem cells into osteoblasts (36)(37)(38). In the present study, the activation of the MAPK signaling pathway was examined in PMA-induced THP-1 cells and it was revealed that the inhibition of P2X7R significantly decreased the phosphorylation of ERK1/2, p38 MAPK and JNK in these macrophages.…”

Section: Discussionmentioning

confidence: 63%

P2X7 receptor regulates EMMPRIN and MMP‑9 expression through AMPK/MAPK signaling in PMA‑induced macrophages

et al. 2018

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The rupture of atherosclerotic plaques may result in the formation of thrombi, which may induce subsequent cardiac events such as acute myocardial infarction. Overproduction of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducers (EMMPRINs) by monocytes and macrophages may lead to rupture of atherosclerotic plaques as a result of the degradation of the extracellular matrix. The purinergic 2X7 receptor (P2X7R) is expressed in macrophages that are assembled in atherosclerotic lesions of human carotid arteries. P2X7R may serve a crucial role in the development of atherosclerosis; therefore, the present study aimed to determine whether P2X7R regulated the expression of EMMPRIN and MMP‑9 in phorbol 12‑myristate 13‑acetate (PMA)‑induced macrophages. In addition, the potential molecular mechanisms involved in this process were investigated. THP‑1 human monocytic cells were pretreated with A‑438079 (a specific inhibitor of P2X7R) for 1 h and subsequently incubated with or without PMA for 48 h. Exposure to A‑438079 significantly decreased the expression of MMP‑9 and EMMPRIN in the PMA‑induced macrophages and attenuated the activation (phosphorylation) of mitogen‑activated protein kinase (MAPK) signaling, including c‑Jun N‑terminal kinase, p38 and extracellular signal‑regulated kinase. The present study also demonstrated that 5'‑AMP‑activated protein kinase (AMPK) was activated by PMA exposure during differentiation from monocytes to macrophages. This activation was reversed by A‑438079 treatment through the inhibition of P2X7R expression. These results suggested that the inhibition of P2X7R may be able to suppress the AMPK/MAPK signaling pathway and consequently downregulate both EMMPRIN and MMP‑9 expression in PMA‑induced macrophages.

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Role of P2×7 receptor in the differentiation of bone marrow stromal cells into osteoblasts and adipocytes

Cited by 37 publications

References 53 publications

Plasma Exosome-derived MicroRNAs as Novel Biomarkers of Traumatic Brain Injury in Rats

Plasma Exosome-derived MicroRNAs as Novel Biomarkers of Traumatic Brain Injury in Rats

How to influence the mesenchymal stem cells fate? Emerging role of ectoenzymes metabolizing nucleotides

P2X7 receptor regulates EMMPRIN and MMP‑9 expression through AMPK/MAPK signaling in PMA‑induced macrophages

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