Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β‐catenin pathways

Yan, Daoguang; Tang, Jiahao; Chen, Liang; Wang, Bingzhang; Weng, She-Ji; Xie, Zhongjie; Wu, Zhiping; Shen, Zhifa; Bai, Bing-Li; Yang, Lei

doi:10.1111/jcmm.14915

Cited by 42 publications

(31 citation statements)

References 50 publications

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“…FGF19 and its receptor FGFR4 are oncogenic drivers of liver cancer and associated with a poor prognosis [ 35 ]. CTNNB1 is generally considered as an intermediate regulator molecule of the FGF19-FGFR4 signaling pathway [ 28 , 36 , 37 , 38 ]. In addition, a lot of studies have shown that the downregulation of CTNNB1 was associated with the downregulations of CDH2, ALCAM and ICAM1, which is consistent with our results [ 31 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ].…”

Section: Resultsmentioning

confidence: 99%

EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide, Inhibits Liver Cancer Cell Growth and Adhesion

Wang

Liu

et al. 2021

Marine Drugs

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The prognosis of liver cancer was inferior among tumors. New medicine treatments are urgently needed. In this study, a novel exopolysaccharide EPS364 was purified from Vibrio alginolyticus 364, which was isolated from a deep-sea cold seep of the South China Sea. Further research showed that EPS364 consisted of mannose, glucosamine, gluconic acid, galactosamine and arabinose with a molar ratio of 5:9:3.4:0.5:0.8. The relative molecular weight of EPS364 was 14.8 kDa. Our results further revealed that EPS364 was a β-linked and phosphorylated polysaccharide. Notably, EPS364 exhibited a significant antitumor activity, with inducing apoptosis, dissipation of the mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS) in Huh7.5 liver cancer cells. Proteomic and quantitative real-time PCR analyses indicated that EPS364 inhibited cancer cell growth and adhesion via targeting the FGF19-FGFR4 signaling pathway. These findings suggest that EPS364 is a promising antitumor agent for pharmacotherapy.

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Section: Resultsmentioning

confidence: 99%

EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide, Inhibits Liver Cancer Cell Growth and Adhesion

Wang

Liu

et al. 2021

Marine Drugs

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“…This means that various physiological functions of type-H endothelial cells can be adopted as potential pharmacological activities of calcitonin family peptides, targeting bone defects, osteoporosis, and even bone metastasis (Singh et al, 2019). Moreover, the present exploration of the AKT-and NF-κB-mediated accumulation and activation of βcatenin not only supplements the mechanisms by which ADM2 and other calcitonin family peptides may potentially regulate osteogenesis and angiogenesis, but also provide novel insights into the relationship between calcitonin family peptides and osteoclastogenesis, except for the cAMP pathway, according to the inhibitory effect of β-catenin signaling on osteoclastogenesis (Yan et al, 2020).…”

Section: Discussionmentioning

confidence: 82%

Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling

Wang

Kong

et al. 2021

Front. Cell Dev. Biol.

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Both osteogenic differentiation and the pro-angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) contribute to bone regeneration during distraction osteogenesis (DO). Adrenomedullin 2 (ADM2), an endogenous bioactive peptide belonging to the calcitonin gene-related peptide family, exhibits various biological activities associated with the inhibition of inflammation and the attenuation of ischemic-hypoxic injury. However, the effects and underlying mechanisms of ADM2 in osteogenic differentiation and the pro-angiogenic potential of BMSCs, along with bone regeneration, remain poorly understood. In the present study, we found that osteogenic induction enhanced the pro-angiogenic potential of BMSCs, and ADM2 treatment further improved the osteogenic differentiation and pro-angiogenic potential of BMSCs. Moreover, the accumulation and activation of β-catenin, which is mediated by the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the activation of protein kinase B (AKT), have been shown to contribute to the effects of ADM2 on BMSCs. In vivo, ADM2 accelerated vessel expansion and bone regeneration, as revealed by improved radiological and histological manifestations and the biomechanical parameters in a rat DO model. Based on the present results, we concluded that ADM2 accelerates bone regeneration during DO by enhancing the osteogenic differentiation and pro-angiogenic potential of BMSCs, partly through the NF-κB/β-catenin and AKT/β-catenin pathways. Moreover, these findings imply that BMSC-mediated coupling of osteogenesis and angiogenesis may be a promising therapeutic strategy for DO patients.

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“…Subsequently, we investigated if the PKC/Akt axis modulates the canonical Wnt signaling pathway. Since GSK3β can be phosphorylated at Ser9 and thus be inactivated by Akt, and—when active—modulate canonical Wnt signaling by promoting the degradation of β-catenin [ 25 ], we first examined the connection between GSK3β phosphorylation and Akt activity in DFCs (Fig. 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, both PKC and Akt are known to interact with the nuclear factor “kappa-light-chain-enhancer” of activated B cells (NF-κB) signaling pathway [ 21 , 22 ], which was shown to regulate the osteogenic differentiation in dental pulp stem cells [ 23 , 24 ]. Another downstream target of Akt is the canonical Wnt signaling pathway as Akt promotes osteogenesis in rat mesenchymal stem cells by phosphorylation of glycogen synthase kinase 3β (GSK3β), which regulates the activity of β-catenin [ 25 ]. The canonical Wnt signaling pathway is also involved in the osteogenic differentiation of human DFCs, albeit with an inhibitory impact [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Classical isoforms of protein kinase C (PKC) and Akt regulate the osteogenic differentiation of human dental follicle cells via both β-catenin and NF-κB

2021

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Background Human dental follicle cells (DFCs) are the precursor cells of the periodontium with a high potential for regenerative therapies of (alveolar) bone. However, the molecular mechanisms of osteogenic differentiation are inadequately understood. Classical isoforms of protein kinase C (PKC) are reported to inhibit osteogenesis of stem/precursor cells. This study evaluated the role of classical PKCs and potential downstream targets on the osteogenic differentiation of DFCs. Methods DFCs were osteogenic differentiated with dexamethasone or bone morphogenetic protein 2 (BMP2). Expression of PKC and potential upstream/downstream regulators was manipulated using activators, inhibitors, and small interfering ribonucleic acid (siRNA). Expression of proteins was examined by Western blot analysis, while the activation levels of enzymes and transcription factors were examined by their phosphorylation states or by specific activation assays. Expression levels of osteogenic markers were examined by RT-qPCR (reverse transcription-quantitative polymerase chain reaction) analysis. Activity of alkaline phosphatase (ALP) and accumulation of calcium nodules by Alizarin Red staining were measured as indicators of mineralization. Results Classical PKCs like PKCα inhibit the osteogenic differentiation of DFCs, but do not interfere with the induction of differentiation. Inhibition of classical PKCs by Gö6976 enhanced activity of Akt after osteogenic induction. Akt was also regulated during differentiation and especially disturbed BMP2-induced mineralization. The PKC/Akt axis was further shown to regulate the canonical Wnt signaling pathway and eventually nuclear expression of active β-catenin during dexamethasone-induced osteogenesis. Moreover, the nuclear factor “kappa-light-chain-enhancer” of activated B cells (NF-κB) pathway is regulated during osteogenic differentiation of DFCs and via the PKC/Akt axis and disturbs the mineralization. Upstream, parathyroid hormone-related protein (PTHrP) sustained the activity of PKC, while Wnt5a inhibited it. Conclusions Our results demonstrate that classical PKCs like PKCα and Akt regulate the osteogenic differentiation of DFCs partly via both β-catenin and NF-κB.

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Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β‐catenin pathways

Cited by 42 publications

References 50 publications

EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide, Inhibits Liver Cancer Cell Growth and Adhesion

EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide, Inhibits Liver Cancer Cell Growth and Adhesion

Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling

Classical isoforms of protein kinase C (PKC) and Akt regulate the osteogenic differentiation of human dental follicle cells via both β-catenin and NF-κB

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