A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis

Bosco, Dale B.; Roycik, Mark D.; Jin, Yongdong; Schwartz, Martin A.; Lively, Ty J.; Zorio, Diego A. R.; Sang, Qing‐Xiang Amy

doi:10.1371/journal.pone.0172925

Cited by 16 publications

(14 citation statements)

References 53 publications

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“…We found the optimal dose of each inhibitor-25 µM of AGA for Runx2 and 10 µM of T0070907 for PPARγ. Previous studies also used the same doses of inhibitors to observe aberrant differentiation [26,30,34,35], which was consistent with our results. Over 25 µM of AGA killed more than 50% of cells due to the cytotoxicity of this inhibitor.…”

Section: Discussionsupporting

confidence: 92%

“…We think that this phenomenon might be due to the cytotoxicity of this inhibitor. Furthermore, both AGA and T0070907 have a tendency to inhibit cell proliferation capacity because of their cytotoxicity [31,34]. of 14 For the same mechanism, in the case of TDSCs from tendinopathy, AGA and T0070907 might inhibit the proliferative capacity as well.…”

Section: Discussionmentioning

confidence: 99%

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Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy

Kim

Chang

2020

IJMS

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The inhibition of the aberrant differentiation of tendon-derived stem cells (TDSCs) is a major target for the regeneration of damaged tendon tissues, as tendinopathy can be caused by the aberrant differentiation of TDSCs. We investigated whether the possible aberrant differentiation of TDSCs can be prevented by using adequate inhibitors. TDSCs extracted from chemically induced tendinopathy and injury-with-overuse tendinopathy models were cultured with 18α-glycyrrhetinic acid (AGA) and T0070907 to block osteogenic differentiation and adipogenic differentiation, respectively. The optimal dose of AGA decreased the osteogenic-specific marker Runx2 (Runt-related transcription factor 2), and T0070907 blocked the adipogenic-specific marker peroxisome proliferator-activated receptor gamma (PPARγ) in mRNA levels. We also found that AGA induced tenogenic differentiation in mRNA levels. However, T0070907 did not affect the tenogenic differentiation and regenerative capacity of TDSCs. We expect that optimal doses of AGA and T0070907 can prevent tendinopathy by inhibiting osteogenic and adipogenic differentiation, respectively. In addition, AGA and T0070907 may play important roles in the treatment of tendinopathy.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy

Kim

Chang

2020

IJMS

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“…Thus, we used western blotting to examine the expression of MMP‐2 and ‐9 and results indicated that TET decreased the expression of MMP‐2 and ‐9 at 24 and 48 hours treatment in GBM 8401 cells. In human malignancies, the increased MMP‐2 and MMP‐9 activities and expression levels are correlated with reduced survival and poor prognosis . It is reported that in human glioblastomas, both MMP‐2 and MMP‐9 are highly expressed and both the messenger RNA and protein levels .…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine inhibits human brain glioblastoma multiforme GBM 8401 cancer cell migration and invasion in vitro

Jiang

Cheng

Kuo

et al. 2018

Environmental Toxicology

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Tetrandrine (TET) has been reported to induce anti-cancer activity in many human cancer cells and also to inhibit cancer cell migration and invasion. However, there are no reports to show TET inhibits cell migration and invasion in human brain glioblastoma multiforme GBM 8401 cells. In this study, we investigated the anti-metastasis effects of TET on GBM 8401 cells in vitro. Under sub-lethal concentrations (from 1, 5 up to 10 μM), TET significantly inhibited cell mobility, migration and invasion of GBM 8401 cells that were assayed by wound healing and Transwell assays. Gelatin zymography assay showed that TET inhibited MMP-2 activity in GBM 8401 cells. Western blotting results indicated that TET inhibited several key metastasis-related proteins, such as p-EGFR (Tyr1068) , SOS-1, GRB2, Ras, p-AKT (Ser473) and p-AKT (Thr308) , NF-κB-p65, Snail, E-cadherin, N-cadherin, NF-κB, MMP-2 and MMP-9 that were significant reduction at 24 and 48 hours treatment by TET. TET reduced MAPK signaling associated proteins such as p-JNK1/2 and p-c-Jun in GBM 8401 cells. The electrophoretic mobility shift (EMSA) assay was used to investigate NF-κB and DNA binding was reduced by TET in a dose-dependently. Based on these findings, we suggested that TET could be used in anti-metastasis of human brain glioblastoma multiforme GBM 8401 cells in the future. K E Y W O R D S GBM 8401 cells, migration and invasion, MMP-2, NF-κB, Tetrandrine (TET) 1 | INTRODUCTION Malignant glioblastoma multiforme (GBM) are the most common and aggressive malignant primary brain tumor in humans and can be a fatal tumor because of difficulties in treating the related metastasis due to the high proliferation rate and invasiveness. 1-5 Currently, the treatment of GBM is the local irradiation, and conventional chemotherapy with temozolomide (TMZ) or surgical resection in combination with radiotherapy and chemotherapy but the median survival rate is only 8-15 months. 4-6 About 20% of patients after treated with TMZ have shown the clinical toxicity. 7 Due to the side effects of TMZ chemotherapy that leading to the limited efficiency. Thus, bases on the Yun-Lian Lin and Jing-Gung Chung contributed equally to this study.

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“…Sc‐WAT and Vis‐WAT derived pre‐adipocytes were pre‐incubated with 10 −5 ‐M T0070907 in differentiation medium for 30 min and then incubated for 2 additional hr with 10 −6 ‐M CCK‐8, and mRNA was extracted ( n = 6; samples were run in duplicate). The dose of T0070907 was selected on the basis of published data describing PPARγ antagonism by T0070907 in adipocytes (Bosco et al, ).…”

Section: Methodsmentioning

confidence: 99%

The cholecystokinin receptor agonist, CCK‐8, induces adiponectin production in rat white adipose tissue

Plaza

Merino

Olmo

et al. 2019

British J Pharmacology

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Background and Purpose:A cholecystokinin (CCK) system has been identified in white adipose tissue (WAT). Nevertheless, the endocrine actions of CCK on WAT remain unknown. Our goal was to investigate the role of CCK in regulating the production of adiponectin, an adipokine expressed in WAT, which is pivotal in preserving energy homeostasis. Experimental Approach:The effect of the bioactive CCK fragment CCK-8 on adiponectin production was studied both in vivo and in vitro. CCK-8 effects were characterized in rats treated with selective CCK 1 and CCK 2 receptor antagonists as well as in pre-adipocytes carrying the selective silencing of either CCK 1 or CCK 2 receptors. The influence of insulin on CCK-8 responses was also analysed. Key Results: In WAT, CCK-8 increased plasma adiponectin levels and the expression of the adiponectin gene (Adipoq). In pre-adipocytes, CCK-8 up-regulated adiponectin production. CCK-8 effects were abolished by L-365,260, a selective CCK 2 receptor antagonist. CCK 2 receptor knockdown also abolished the effects of CCK-8 in pre-adipocytes. Moreover, in vitro CCK-8 effects were blocked by triciribine, a specific inhibitor of protein kinase B (Akt) and by the PPARγ antagonist T0070907. Silencing the expression of the insulin receptor inhibited CCK-8-induced Adipoq expression in pre-adipocytes. Furthermore, insulin potentiated the effect of CCK-8. Conclusion and Implications: CCK-8 stimulates adiponectin production in WAT by acting on CCK 2 receptors, through a mechanism involving both Akt and PPARγ. Moreover, CCK-8 actions are only observed in the presence of insulin. Our results could have translational value in the design of new insulin-sensitizing therapies.

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A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis

Cited by 16 publications

References 53 publications

Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy

Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy

Tetrandrine inhibits human brain glioblastoma multiforme GBM 8401 cancer cell migration and invasion in vitro

The cholecystokinin receptor agonist, CCK‐8, induces adiponectin production in rat white adipose tissue

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