Obesity enhances the recruitment of mesenchymal stem cell to visceral adipose tissue

2021 ◽  
Author(s):  
Agatha Assis-Ferreira ◽  
Roberta F.g. Saldanha-Gama ◽  
Natalia M de Brito ◽  
Mariana Renovato-Martins ◽  
Rafael L Simões ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissues ◽  
Migratory Response ◽  
Migratory Activity ◽  
Diet Induced Obesity ◽  
Pathway Activation ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells ◽  
Spontaneous Migration ◽  
Visceral Adipose

In obesity, high levels of TNF-α in the bone marrow microenvironment induces the bone marrow-mesenchymal stem cells (BM-MSCs) towards a pro-adipogenic phenotype. Here, we investigated the effect of obesity on the migratory potential of BM-MSCs and their fate towards the adipose tissues. BM-MSCs were isolated from male C57Bl/06 mice with high-fat diet-induced obesity. The migratory potential of the BM-MSCs, their presence in the subcutaneous (SAT) and the visceral adipose tissues (VAT), and the possible mechanisms involved were investigated. Obesity did not affect MSC content in the bone marrow but increased the frequency of MSCs in blood, SAT, and VAT. In these animals, the SAT adipocytes presented a larger area, without any changes in adipokine production or the SDF-1α gene expression. In contrast, in VAT, obesity increased leptin and IL-10 levels but did not modify the size of the adipocytes. The BM-MSCs from obese animals presented increased spontaneous migratory activity. Despite the augmented expression of CXCR4, these cells exhibited decreased migratory response toward SDF-1α, compared to that of BM-MSCs from lean mice. The PI3K-AKT pathway activation seems to mediate the migration of BM-MSCs from lean mice, but not from obese mice. Additionally, we observed an increase in the spontaneous migration of BM-MSCs from lean mice when they were co-cultured with BM-HCs from obese animals, suggesting a paracrine effect. We concluded that obesity increased the migratory potential of the BM-MSCs and induced their accumulation in VAT, which may represent an adaptive mechanism in response to chronic nutrient overload.

Concentrations of Metalloproteinased-9 (MMP-9), Metalloproteinases -1 and-2 Tissue Inhibitors (TIMP-1, TIMP-2), Tumor Necrosis Factor-α (TNF-α), Hepatocyte Growth Factor (HGF), Dickkopf Related Proten 1 (DKK-1) and Emmprin (CD147) Expression Are Increased in Patients with Myeloma Multiplex and MMP-9 Correlates with advanced Stage of Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5069-5069
Author(s):  
Donata Urbaniak-Kujda ◽  
Katarzyna Kapelko-Slowik ◽  
Dariusz Wolowiec ◽  
Jaroslaw Dybko ◽  
Iwona Prajs ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Culture Supernatant ◽  
Control Group ◽  
Advanced Stage ◽  
Tnf Α ◽  
Cd147 Expression ◽  
Marrow Mesenchymal Stem Cells ◽  
Mean Concentration ◽  
Healthy Persons

Abstract Abstract 5069 Introduction. Metalloproteinases (MMP) belong to the group of metallodependent proteolitic enzymes included into endopeptidases being characteristic for the ability of extracelullar matrix degradation. Gelatinases: A(MMP-2) and B (MMP-9) take part in neoplasms metastatic process. MMP activity is controlled both by their tissue inhibitors (TIMP) and activator (emmprin). Multiple myeloma (MM) is a lymphocytes B proliferative disease which is accompanied by osteolytic lesions and extramedullar spread. There are few reports concerning the assessment of MMP-2, MMP-9, TIMP-1, TIMP-2, TNF-α, HGF, DKK-1 concentrations as well as emmprin expression on bone marrow mesenchymal stem cells (BMSC) in patients suffering from multiple myeloma. Aim. The goal of the study was to assess MMP-2, MMP-9, TIMP-1,TIMP-2, TNF-α, HGF, DKK-1 concentrations in marrow plasma, in culture supernatant as well as emmprin expression on BMSC in multiple myeloma patients. The survey also comprised metalloproteinases, their inhibitors and cytokines influence on myeloma development and progress and included the trial whether these parameters are related to clinical stage of myeloma. Patients and methods. Forty patients were enrolled in the study: 18 males and 22 females aged 48–81 years (mean age-52.4 years) with de novo diagnosed multiple myeloma. According to ISS (International Staging System) 7 patients were at stage I, 19 patients were at stage II and 14 patients were at stage III. Control group consisted of 11 healthy persons matched with age and sex. Bone marrow was collected before the treatment. Bone marrow mesenchymal stem cells (BMSCs) revealing antigen CD166 expression were derived in incubation process on Mesencult culture. Concentrations: MMP-2 and TIMP-2, MMP-9, TIMP-1, TNF-α, HGF and DKK-1 were measured in marrow plasma and culture supernatant with ELISA test. Emmprin expression on CD166+ cells was assessed by FACS analysis. Results. Mean concentrations of MMP-9, TIMP-1 and TIMP-2 in both marrow plasma and culture supernatant were significantly higher in multiple myeloma patients in comparison with control group. Mean concentration of TNF-α, HGF and DKK-1 assessed in culture supernatant were significantly higher in patients than in control group. In turn, MMP-2 mean concentration in marrow plasma did not differ significantly between patients and control groups. MMP-9/TIMP-1 ratio for marrow plasma and supernatant was significantly higher in MM group. MMP-2/TIMP-2 ratio for culture supernatant was higher in patients in comparison with healthy persons. Besides, in patients at the higher stage of the disease progress (II+III), MMP-9 concentration estimated in marrow plasma was higher than in patients placed at the disease advance low stage (I). CD147 expression on BMSC cells of myeloma patients was significantly higher than the one on BMSC collected from healthy persons. It also correlated with MMP-2 and TIMP-2 concentrations and MMP-2/TIMP-2 ratio in culture supernatant. Conclusions. Concentrations of MMP-9, MMP-2, TIMP-1, TIMP-2, TNF-α, HGF and DKK-1 and emmprin expression are increased in myeloma patients and concentration of MMP-9 correlates with advanced stage of disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Nogo-A Is Critical for Pro-Inflammatory Gene Regulation in Myocytes and Macrophages

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 282
Author(s):  
H. M. Arif Ullah ◽  
A. K. Elfadl ◽  
SunYoung Park ◽  
Yong Deuk Kim ◽  
Myung-Jin Chung ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Murine Model ◽  
Muscle Diseases ◽  
Migratory Activity ◽  
Homologous Protein ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Als Patients ◽  
Lps Treatment

Nogo-A (Rtn 4A), a member of the reticulon 4 (Rtn4) protein family, is a neurite outgrowth inhibitor protein that is primarily expressed in the central nervous system (CNS). However, previous studies revealed that Nogo-A was upregulated in skeletal muscles of Amyotrophic lateral sclerosis (ALS) patients. Additionally, experiments showed that endoplasmic reticulum (ER) stress marker, C/EBP homologous protein (CHOP), was upregulated in gastrocnemius muscle of a murine model of ALS. We therefore hypothesized that Nogo-A might relate to skeletal muscle diseases. According to our knocking down and overexpression results in muscle cell line (C2C12), we have found that upregulation of Nogo-A resulted in upregulation of CHOP, pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while downregulation of Nogo-A led to downregulation of CHOP, IL-6 and TNF-α. Immunofluorescence results showed that Nogo-A and CHOP were expressed by myofibers as well as tissue macrophages. Since resident macrophages share similar functions as bone marrow-derived macrophages (BMDM), we therefore, isolated macrophages from bone marrow to study the role of Nogo-A in activation of these cells. Lipopolysaccharide (LPS)-stimulated BMDM in Nogo-KO mice showed low mRNA expression of CHOP, IL-6 and TNF-α compared to BMDM in wild type (WT) mice. Interestingly, Nogo knockout (KO) BMDM exhibited lower migratory activity and phagocytic ability compared with WT BMDM after LPS treatment. In addition, mice experiments data revealed that upregulation of Nogo-A in notexin- and tunicamycin-treated muscles was associated with upregulation of CHOP, IL-6 and TNF-α in WT group, while in Nogo-KO group resulted in low expression level of CHOP, IL-6 and TNF-α. Furthermore, upregulation of Nogo-A in dystrophin-deficient (mdx) murine model, myopathy and Duchenne muscle dystrophy (DMD) clinical biopsies was associated with upregulation of CHOP, IL-6 and TNF-α. To the best of our knowledge, this is the first study to demonstrate Nogo-A as a regulator of inflammation in diseased muscle and bone marrow macrophages and that deletion of Nogo-A alleviates muscle inflammation and it can be utilized as a therapeutic target for improving muscle diseases.

Effects of Melatonin on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in Inflammatory Environment by Regulating Mammalian Target of Rapamycin/Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling

2021 ◽  
Vol 11 (4) ◽  
pp. 749-755
Author(s):  
Chi Zhang ◽  
Yuanhe Wang ◽  
Kang Sun ◽  
Dingzhu Yu ◽  
Shaoqi Tian
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Sod Activity ◽  
Alp Activity ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells

Human bone marrow mesenchymal stem cells (BMSCs) differentiation into special cell types is affected by inflammation. Melatonin has various effects such as anti-oxidation and immune regulation. However, melatonin’s effect on BMSCs osteogenic differentiation during inflammation has not been elucidated. Rat BMSCs were isolated and assigned into control group, inflammation group (1 μg/ml lipopolysaccharide, LPS) and melatonin group (100 μM melatonin was added to LPSstimulated BMSCs cells) followed by analysis of BMSCs proliferation by MTT assay, Caspase 3 and ALP activity, expression of Runx2 and OP by Real time PCR, ROS content and SOD activity, TNF-α and IL-1β secretion by ELISA and mTOR/PI3K/AKT signaling protein level by Western blot. LPS action on BMSCs significantly inhibits BMSCs proliferation, promotes Caspase 3 activity, inhibits ALP activity, decreases Runx2 and OP expression and SOD activity, increases ROS content and TNF-α and IL-1β secretion as well as reduced mTOR and p-PI3K level (P <0.05). Melatonin addition significantly reversed the above changes (P <0.05). Melatonin can regulate oxidative stress, inhibit inflammation, and promote BMSCs proliferation and osteogenic differentiation in inflammatory environment by activating mTOR/PI3K/AKT signaling pathway.

A High-Fat Diet Increases IL-1, IL-6, and TNF-α Production by Increasing NF-κB and Attenuating PPAR-γ Expression in Bone Marrow Mesenchymal Stem Cells

Inflammation ◽  
2012 ◽  
Vol 36 (2) ◽  
pp. 379-386 ◽  
Author(s):  
Mayara Cortez ◽  
Luciana Simão Carmo ◽  
Marcelo Macedo Rogero ◽  
Primavera Borelli ◽  
Ricardo Ambrósio Fock
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
High Fat Diet ◽  
High Fat ◽  
Ppar Γ ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Effects of inhalation and intravenous administration of allogeneic mesenchymal bone marrow stromal cells in a bleomycin-induced model of pulmonary fibrosis in rabbits

2018 ◽  
Vol 19 (4) ◽  
pp. 88-96
Author(s):  
A. V. Averyanov ◽  
A. G. Konoplyannikov ◽  
F. G. Zabozlaev ◽  
O. V. Danilevskaya ◽  
M. A. Konoplyannikov ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Stromal Cells ◽  
Treated Group ◽  
Control Group ◽  
Therapeutic Effects ◽  
Treatment Groups ◽  
Tnf Α ◽  
The Standard Model ◽  
Marrow Mesenchymal Stem Cells ◽  
Tgf Β1

Aim:to perform a comparative analysis of the effi cacy of the inhaled and intravenous delivery of equivalent doses of bone marrow mesenchymal stem cells (BMMSCs) in rabbits according to the standard model of bleomycin pulmonary fi brosis.Materials and methods.After bronchoscopic instillation of bleomycin, 5 rabbits received intravenous transplantation of 2 × 106 allogeneic BMMSCs, other 5 rabbits – 2 × 107 MSCs inhaled via compressor nebulizer; control healthy and bleomycin group included 5 animals each.Results.Both groups treated with BMMSCs had a signifi cantly lower Ashcroft fi brosis index than the bleomycin control group. Expression of collagen in lung tissue in all groups with bleomycin injury was superior to healthy controls, but in animals underwent intravenous BMMSC transplantation collagen score was 0.74 points, and in inhaled treated group – 0.51 points, while in bleomycin controls – 2.1 point. Levels of TNF-α and TGF-β1 in BAL fl uids tended to decrease in treatment groups, but did not differ signifi cantly from control. A similar picture was observed in the cytological analysis of BAL.Conclusion.In general, both methods of delivering of BMMSCs to the lungs demonstrated similar therapeutic effects in inhibiting the development of experimental fi brosis, indicating that both intravenous and inhalational way of introduction can be used for subsequent clinical studies. 

scholarly journals Bone marrow mesenchymal stem cells stimulated by TNF-α enhance the apoptosis of hepatic stellate cells

2012 ◽  
Vol 20 (19) ◽  
pp. 1713
Author(s):  
Xian-Ke Luo ◽  
Zheng-Feng Lu ◽  
Hai-Xing Jiang ◽  
Shan-Yu Qin ◽  
Guo-Zhong Chen
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells
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