Activated<i>NF-κB</i>in Bone Marrow Mesenchymal Stem Cells from Systemic Lupus Erythematosus Patients Inhibits Osteogenic Differentiation Through Downregulating Smad Signaling

Tang, Yang; Xie, Hao; Chen, Jinyun; Geng, Linyu; Chen, Haifeng; Li, Xia; Hou, Yayi; Lu, Liwei; Shi, Songtao; Zeng, Xiaofeng; Sun, Lingyun

doi:10.1089/scd.2012.0226

Cited by 70 publications

(56 citation statements)

References 60 publications

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“…The activated R-Smads bind to the common Smad (Co-Smad, Smad4) to form complex, and then translocates to the nucleus along with a number of transcription factors to regulate the expression of target genes (13). BMPs can also activate the non-canonical Smad pathways, such as PI3K/Akt, mitogenactivated protein kinase (MAPK) and nuclear factor κB (NF-κB) (36)(37)(38). In the present study, we found that Res can increase the level of BMP7 in HCT116 cells, which implied that the anticancer activity of Res may arise from upregulating the expression of BMP7.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells

et al. 2017

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Abstract. Colon cancer is common worldwide and accounts for the significant cancer related morbidity and mortality in patients. Although extensive advancement has been made in colon cancer treatment and diagnosis in the last decades, there is still a giant gap between the clinical expectation. It has been reported that resveratrol (Res) may be a potential candidate for cancer treatment. However, the specific mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Res in human colon cancer cells, and unveiled the possible mechanism for this effect. With cell viability, flow cytometry, PCR and western blot analysis, we demonstrated the efficacious anticancer activity of Res in HCT116 cells. Mechanically, we found that Res greatly upregulates BMP7 in HCT116 cells. Exogenous BMP7 enhances the anticancer effect of Res in HCT116 cells, which was almost reversed by the BMP7 specific antibody. Res does not activate the BMPs/Smads signaling, but decreases the phosphorylation of Akt1/2/3 substantially in HCT116 cells. Exogenous BMP7 enhances the inhibitory effect of Res on the phosphorylation of Akt1/2/3, while BMP7 immunodepletion reverses this effect notably. Res markedly decreases the phosphorylation of PTEN, which can be enhanced by exogenous BMP7 but partly reversed by the BMP7 antibody. Our findings suggested that Res may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating BMP7 to decrease, at least, the phosphorylation of

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Section: Discussionmentioning

confidence: 99%

Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells

et al. 2017

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“…Recent research showed that there were abnormalities in actin cytoskeleton, cell cycling regulation, BMP/TGF-β, and MAPK signaling pathways in BM-MSCs from SLE patients [177]. Tang et al found that activated NF-κB pathway in SLE derived BM-MSCs inhibits the BMP-2-induced osteoblastic differentiation through BMP/Smad signaling pathway, suggesting that the impaired osteoblastic differentiation may participate in the pathology of osteoporosis in SLE patients [178]. Another research also found that BM-MSCs from SLE patients exhibited senescent behavior and are involved in the pathogenesis of SLE.…”

Section: Mscs and Slementioning

confidence: 99%

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

Zhao¹,

Ren

Han

2016

Journal of Cellular Immunotherapy

258

200

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Mesenchymal stem cells (MSCs) represent a heterogenous population of adult,fibroblast-like multi-potent cells. MSCs have drawn much attention during the last decade in the field of regenerative medicine, mainly due to their capacity to differentiate into specific cell types, abundant production of soluble growth factors and cytokines, and hematopoiesis supporting properties. In addition, MSCs can migrate to the sites of inflammation and hold potent of immunomodulatory and anti-inflammatory effects through cell and cell interactions between MSCs and lymphocytes or production of soluble factors. Therefore, the application of MSCs in many disease situations is full of possibilities for future clinical treatment. Phase III clinical trials have been run using

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“…In their study, the differentiation potential was evaluated only microscopically, which did not allow them to obtain quantitative data. In a study by Tang et al, 26 reduced differentiation into osteoblasts of MSCs isolated from patients suffering from systemic lupus was detected.…”

Section: Discussionmentioning

confidence: 96%

Characterisation of mesenchymal stem cells from patients with amyotrophic lateral sclerosis

Matejckova¹,

Zajı́cová

Heřmánková³

et al. 2018

J Clin Pathol

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AimsMesenchymal stem cells (MSCs) have recently been tested in clinical trials to treat severe diseases, including amyotrophic lateral sclerosis (ALS). Since autologous MSCs are frequently used for therapy, we aimed to evaluate the possible influence of the disease on characteristics and function of these cells.MethodsMSCs were isolated from the bone marrow of patients with ALS and compared with MSCs from healthy controls (HC). The cells were tested for phenotype, growth properties, differentiation ability, metabolic activity, secretory potential, expression of genes for immunomodulatory molecules and for the ability to regulate proliferation of mitogen-stimulated peripheral blood leucocytes. MSCs from patients with ALS and HC were either unstimulated or treated with proinflammatory cytokines for 24 hours before testing.ResultsMSCs isolated from patients with ALS have a higher differentiation potential into adipocytes, express elevated levels of mRNA for interleukin-6, but produce less hepatocyte growth factor than MSCs from HC. On the other hand, there were no significant differences between MSCs from patients with ALS and HC in the expression of phenotypic markers, growth properties, metabolic activity, osteogenic differentiation potential and immunoregulatory properties.ConclusionsThe results suggest that, in spite of some differences in cytokine production, MSCs from patients with ALS can be useful as autologous cells in therapy of ALS.

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ActivatedNF-κBin Bone Marrow Mesenchymal Stem Cells from Systemic Lupus Erythematosus Patients Inhibits Osteogenic Differentiation Through Downregulating Smad Signaling

Cited by 70 publications

References 60 publications

Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells

Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

Characterisation of mesenchymal stem cells from patients with amyotrophic lateral sclerosis

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