Melatonin promotes the BMP9-induced osteogenic differentiation of mesenchymal stem cells by activating the AMPK/β-catenin signalling pathway

Jiang, Tianyuan; Xia, Chao; Rothenberg, Marc E.; Hu, Yan; Wang, Yan; Wu, Jin; Chen, Shuyan; Gao, Yanhong

doi:10.1186/s13287-019-1511-7

Cited by 40 publications

(40 citation statements)

References 57 publications

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“…In this regard, MSCs pulsed with tumor-derived microvesicles showed an enhanced antitumor activity in HCC [ 166 ]. Some previous report revealed the use of melatonin enhanced the potential therapeutic role MSCs in treatment various diseases such as acute kidney injury, metabolic syndromes including diabetes through various mechanisms that include through the activation of antioxidative pathways, inhibition of the inflammatory response and reduction of apoptosis and fibrosis [ 19 , 167 , 168 , 169 , 170 ]. More interestingly, few recent reports revealed the beneficial effects of the combination between melatonin and MSCs on targeting inflammation in HCC [ 171 , 172 , 173 , 174 , 175 ].…”

Section: Potential Beneficial Effect Of the Combination Between Mementioning

confidence: 99%

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Elmahallawy

Mohamed

Abdo

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) is the most common hepatobiliary malignancy with limited therapeutic options. On the other hand, melatonin is an indoleamine that modulates a variety of potential therapeutic effects. In addition to its important role in the regulation of sleep–wake rhythms, several previous studies linked the biologic effects of melatonin to various substantial endocrine, neural, immune and antioxidant functions, among others. Furthermore, the effects of melatonin could be influenced through receptor dependent and receptor independent manner. Among the other numerous physiological and therapeutic effects of melatonin, controlling the survival and differentiation of mesenchymal stem cells (MSCs) has been recently discussed. Given its controversial interaction, several previous reports revealed the therapeutic potential of MSCs in controlling the hepatocellular carcinoma (HCC). Taken together, the intention of the present review is to highlight the effects of melatonin and mesenchymal stem cells as a key for functional integrity for liver cancer treatment. We hope to provide solid piece of information that may be helpful in designing novel drug targets to control HCC.

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Section: Potential Beneficial Effect Of the Combination Between Mementioning

confidence: 99%

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Elmahallawy

Mohamed

Abdo

et al. 2020

IJMS

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“…In addition, it is reported that polydatin improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of β-catenin pathway [39] . Melatonin promotes the BMP9-induced osteogenic differentiation of mesenchymal stem cells by activating the β-catenin signalling pathway [40] . But inactivation of β-catenin signaling in osteoblasts causedthe increased osteoclastogenesis due to insu cient production of OPG [41] .…”

Section: Discussionmentioning

confidence: 99%

Osthole Inhibits Osteoclast Formation and Enhances Bone Mass of Bone Marrow Mesenchymal Stem cells by Activating β-catenin-OPG Signaling Pathway

Jin¹,

Liao²,

Da³

et al. 2020

Preprint

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Summary Osthole has potential therapeutic applications due to its antiosteoporotic. Our study suggested that osthole attenuates osteoclast formation by stimulating the activation of β-catenin-OPG signaling and could be a potential agent to inhibit bone resorption. Introduction Osthole has potential therapeutic applications due to its antiosteoporotic. we performed study to test if OPG is the target gene of osthole-attenuated osteoclastogenesis. Methods In vivo, using 12-month-old male mice to evaluate the effect of osthole on bone mass. In vitro, Bone marrow stem cells (BMSCs) were isolated, extracted from 3-month-old C57BL/6J mice, 3-month-old β-cateninfx/fx mice, or 3-month-old OPG−/− mice and its littermates of OPG+/+ mice. Results we found that osthole significantly increased the gene and protein levels of OPG expression in primary BMSCs dose-dependently. The deletion of the OPG gene did not affect β-catenin expression and the deletion of the β-catenin gene inhibited OPG expression in BMSCs, which indicated that osthole stimulated the expression of OPG through activation of β-catenin signaling. Conclusion Osthole attenuates osteoclast formation by stimulating the activation of β-catenin-OPG signaling and could be a potential agent to inhibit bone resorption.

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“…Alizarin Red and Alkaline phosphatase ( ALP) staining were performed according to a previously described procedure ( 17 ).…”

Section: Methodsmentioning

confidence: 99%

The p53/miR-145a Axis Promotes Cellular Senescence and Inhibits Osteogenic Differentiation by Targeting Cbfb in Mesenchymal Stem Cells

et al. 2021

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The osteogenic differentiation capacity of senescent bone marrow mesenchymal stem cells (MSCs) is reduced. p53 not only regulates cellular senescence but also functions as a negative regulator in bone formation. However, the role of p53 in MSCs senescence and differentiation has not been extensively explored. In the present study, we investigated the molecular mechanism of p53 in MSCs senescence and osteogenic differentiation. We found that p53 was upregulated during cellular senescence and osteogenic differentiation of MSCs respectively induced by H2O2 and BMP9. Similarly, the expression of p53-induced miR-145a was increased significantly. Furthermore, Overexpression of miR-145a in MSCs promoted cellular senescence and inhibited osteogenic differentiation. Then, we identified that p53-induced miR-145a inhibited osteogenic differentiation by targeting core binding factor beta (Cbfb), and the restoration of Cbfb expression rescued the inhibitory effects of miRNA-145a. In summary, our results indicate that p53/miR-145a axis exert its functions both in promoting senescence and inhibiting osteogenesis of MSCs, and the novel p53/miR-145a/Cbfb axis in osteogenic differentiation of MSCs may represent new targets in the treatment of osteoporosis.

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Melatonin promotes the BMP9-induced osteogenic differentiation of mesenchymal stem cells by activating the AMPK/β-catenin signalling pathway

Cited by 40 publications

References 57 publications

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Melatonin and Mesenchymal Stem Cells as a Key for Functional Integrity for Liver Cancer Treatment

Osthole Inhibits Osteoclast Formation and Enhances Bone Mass of Bone Marrow Mesenchymal Stem cells by Activating β-catenin-OPG Signaling Pathway

The p53/miR-145a Axis Promotes Cellular Senescence and Inhibits Osteogenic Differentiation by Targeting Cbfb in Mesenchymal Stem Cells

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