scholarly journals Interleukin-6 Knockout Inhibits Senescence of Bone Mesenchymal Stem Cells in High-Fat Diet-Induced Bone Loss

2021 ◽  
Vol 11 ◽  
Author(s):  
Yujue Li ◽  
Lingyun Lu ◽  
Ying Xie ◽  
Xiang Chen ◽  
Li Tian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
Interleukin 6 ◽  
High Fat Diet ◽  
Cell Senescence ◽  
Low Grade ◽  
High Fat ◽  
Bone Mesenchymal Stem Cells

Obesity, a chronic low-grade inflammatory state, not only promotes bone loss, but also accelerates cell senescence. However, little is known about the mechanisms that link obesity, bone loss, and cell senescence. Interleukin-6 (IL-6), a pivotal inflammatory mediator increased during obesity, is a candidate for promoting cell senescence and an important part of senescence-associated secretory phenotype (SASP). Here, wild type (WT) and (IL-6 KO) mice were fed with high-fat diet (HFD) for 12 weeks. The results showed IL-6 KO mice gain less weight on HFD than WT mice. HFD induced trabecular bone loss, enhanced expansion of bone marrow adipose tissue (BMAT), increased adipogenesis in bone marrow (BM), and reduced the bone formation in WT mice, but it failed to do so in IL-6 KO mice. Furthermore, IL-6 KO inhibited HFD-induced clone formation of bone marrow cells (BMCs), and expression of senescence markers (p53 and p21). IL-6 antibody inhibited the activation of STAT3 and the senescence of bone mesenchymal stem cells (BMSCs) from WT mice in vitro, while rescued IL-6 induced senescence of BMSCs from IL-6 KO mice through the STAT3/p53/p21 pathway. In summary, our data demonstrated that IL-6 KO may maintain the balance between osteogenesis and adipogenesis in BM, and restrain senescence of BMSCs in HFD-induced bone loss.

scholarly journals CXCL2 Impairs Functions of Bone Marrow Mesenchymal Stem Cells and Can Serve as a Serum Marker in High-Fat Diet-Fed Rats

2021 ◽  
Vol 9 ◽  
Author(s):  
Jianhai Bi ◽  
Qiuchen Li ◽  
Zhigang Yang ◽  
Lei Cai ◽  
Tao Lv ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Serum Marker ◽  
Cytokine Signaling ◽  
Low Grade ◽  
High Fat

In modern society excessive consumption of a high-fat diet (HFD) is a significant risk factor for many diseases such as diabetes, osteoarthritis and certain cancers. Resolving cellular and molecular mechanisms underlying HFD-associated disorders is of great importance to human health. Mesenchymal stem cells (MSCs) are key players in tissue homeostasis and adversely affected by prolonged HFD feeding. Low-grade systemic inflammation induced by HFD is characterized by increased levels of pro-inflammatory cytokines and alters homeostasis in many organs. However, whether, which and how HFD associated inflammatory cytokines impair MSCs remain unclear. Here we demonstrated that HFD induced serum cytokines disturbances, especially a continuous elevation of serum CXCL2 level in rats. Coincidentally, the differentially expressed genes (DEGs) of bone marrow MSCs (BMSCs) which functions were impaired in HFD rats were enriched in cytokine signaling. Further mechanism analysis revealed that CXCL2 treatment in vitro suppresses the adipogenic potential of BMSCs via Rac1 activation, and promoted BMSC migration and senescence by inducing over-production of ELMO1 and reactive oxygen species (ROS) respectively. Moreover, we found that although glycolipid metabolism indicators can be corrected, the CXCL2 elevation and BMSC dysfunctions cannot be fully rescued by diet correction and anti-inflammatory aspirin treatment, indicating the long-lasting deleterious effects of HFD on serum CXCL2 levels and BMSC functions. Altogether, our findings identify CXCL2 as an important regulator in BMSCs functions and may serve as a serum marker to indicate the BMSC dysfunctions induced by HFD. In addition, our findings underscore the intricate link among high-fat intake, chronic inflammation and BMSC dysfunction which may facilitate development of protective strategies for HFD associated diseases.

scholarly journals Metabolic and Pancreatic Effects of Bone Marrow Mesenchymal Stem Cells Transplantation in Mice Fed High-Fat Diet

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0124369 ◽  
Author(s):  
Patricia de Godoy Bueno ◽  
Juliana Navarro Ueda Yochite ◽  
Graziela Fernanda Derigge-Pisani ◽  
Kelen Cristina Ribeiro Malmegrim de Farias ◽  
Lucimar Retto da Silva de Avó ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
High Fat Diet ◽  
High Fat ◽  
Marrow Mesenchymal Stem Cells ◽  
Stem Cells Transplantation

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

High-carbohydrate, High-fat Diet-induced Hyperlipidemia Hampers the Differentiation Balance of Bone Marrow Mesenchymal Stem Cells by Suppressing Autophagy via the AMPK/ mTOR Pathway in Rat Models

2020 ◽  
Author(s):  
Zhenzhen Shang ◽  
Ting Zhang ◽  
Mengyang Jiang ◽  
Xiaojie Yin ◽  
Hui Qiang Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Metabolism ◽  
High Fat Diet ◽  
High Fat ◽  
Rat Models ◽  
High Carbohydrate ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Disorders of bone metabolism caused by hyperlipidemia is not conducive to osseointegration of implants. Autophagy, an evolutionarily conserved, lysosomal-mediated degradation process, is indispensable for bone homeostasis, its effects on hyperlipidemia-induced osteoporosis remain to be elucidated. The objective of this study was to determine whether autophagy affects bone metabolism and implant osseointegration through regulating the function of bone marrow mesenchymal stem cells (BMMSCs) in rats with hyperlipidemia and to confirm signaling pathway involved in the regulation of autophagy. Methods: Hyperlipidemia models were established through a long-term high-carbohydrate, high-fat diet in 6-week-old male Sprague-Dawley rats. The impact of hyperlipidemia on bone metabolism and early osseointegration of implants was explored by the methods including serum biochemical detection, micro-computed tomography and bone morphology detection. Biological properties and autophagy levels of BMMSCs were also determined. Further, we determined if autophagy was involved in bone metabolism changes resulting from high-fat diet by focusing on the lineage differentiation of BMMSCs. The signaling pathway involved in the regulation of autophagy was also explored.Results: The high-carbohydrate, high-fat diet (HCHF) was given to the rats for seven months aggravated bone loss in the cancellous bone and reduced osseointegration of implants. BMMSCs from hyperlipidemia rats exhibited decreased osteogenesis, increased adipogenesis and decreased autophagic activity compared with regular diet (RD) BMMSCs. Rapamycin treatment restored the impaired osteogenic differentiation and inhibited the adipogenic differentiation of HCHF-BMMSCs through the activation of autophagy. Further, AMPK/mTOR signaling pathways was related to the impairment of autophagy of HCHF-BMMSCs. Conclusions: Our data indicate that long-term high-carbohydrate, high-fat diet-induced hyperlipidemia hampers the differentiation balance of bone marrow mesenchymal stem cells by suppressing autophagy via the AMPK/ mTOR pathway, which ultimately led to aggravated bone loss in the cancellous bone and reduced osseointegration of implants in rat models.

BONE CELLS UNDER MICROGRAVITY

2013 ◽  
Vol 13 (05) ◽  
pp. 1340006 ◽  
Author(s):  
PENG SHANG ◽  
JIAN ZHANG ◽  
AIRONG QIAN ◽  
JINGBAO LI ◽  
RUI MENG ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Microgravity Environment ◽  
Human Beings ◽  
Bone Mesenchymal Stem Cells ◽  
Skeleton Structure

Weightlessness environment (also microgravity) during the exploration of space is the major condition which must be faced by astronauts. One of the most serious adverse effects on astronauts is the weightlessness-induced bone loss due to the unbalanced bone remodeling. Bone remodeling of human beings has evolved during billions of years to make bone tissue adapt to the gravitational field of Earth (1g) and maintain skeleton structure to meet mechanical loading on Earth. However, under weightlessness environment the skeleton system no longer functions against the pull of gravity, so there is no necessity to keep bone strong enough to support the body's weight. Therefore, the balance of bone remodeling is disrupted and bone loss occurs, which is extremely deleterious to an astronaut's health during long-term spaceflight. Bone remodeling is mainly orchestrated by bone mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. Here, we review how these bone cells respond to microgravity environment.

HIGH GLUCOSE INDUCED BONE LOSS VIA ATTENUATING THE PROLIFERATION AND OSTEOBLASTOGENESIS AND ENHANCING ADIPOGENESIS OF BONE MARROW MESENCHYMAL STEM CELLS

2013 ◽  
Vol 25 (05) ◽  
pp. 1340010 ◽  
Author(s):  
Wen-Tyng Li ◽  
Wen-Kai Hu ◽  
Feng-Ming Ho
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Bone Loss ◽  
High Glucose ◽  
Chromatin Condensation ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Bone Marrow Mscs

Diabetes mellitus (DM) is associated with bone loss and leads to osteopenia and osteoporosis. This study was undertaken to investigate whether the impaired functions of mesenchymal stem cells (MSCs) derived from bone marrow play a role in pathogenesis of DM-associated bone loss. Bone marrow MSCs were taken from the alloxan-induced diabetic rats and normal rats. Bone mineral densities of tibias and femurs in diabetic rats decreased compared to those of normal rats as shown by dual energy X-ray absorptiometry. MSCs from diabetic rats exhibited reduced colony formation activity. The in vitro effects of high glucose (HG) (20 or 33 mM) on the growth, oxidative stress, apoptosis, and differentiation MSCs were next assessed. The viability and proliferation of MSCs derived from diabetic rats decreased significantly compared with that from normal rats. HG further suppressed the proliferation and viability of MSCs from both diabetic and normal rats. HG was associated with 38–40% increase in reactive oxygen species level and had significantly downregulated the activities of superoxide dismutase (SOD) and catalase (CAT) which could be recovered by the addition of L-ascorbic acid. The phenomena of apoptosis such as chromatin condensation and DNA fragmentation were found in cells cultured under HG conditions. As compared with 5.5 mM glucose, exposure of MSCs to HG enhanced adipogenic induction of triacylglycerol accumulation and inhibited osteogenic induction of alkaline phosphatase activity. HG increased peroxisome proliferator-activated receptor gamma expression during adipogenesis and reduced RUNX2 expression during osteoblastogenesis. These results indicate that MSCs derived from diabetic rats exhibited the inhibitory effects on cell growth and osteogenic ability. The oxidative stress, apoptosis, and adipogenic capability of MSCs were increased by HG. Furthermore, it is suggested that HG induces bone loss via attenuating the proliferation and osteoblastogenesis and enhancing adipogenesis mediated by the oxidative stress in rat bone marrow MSCs.

scholarly journals Epigenomic Regulation of SATB2 Links Maternal Obesity to Impaired Osteoblast Differentiation (P11-034-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jin-Ran Chen ◽  
Haijun Zhao ◽  
Oxana P Lazarenko ◽  
Kartik Shankar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Epigenetic Regulation ◽  
High Fat Diet ◽  
Osteoblast Differentiation ◽  
Maternal Obesity ◽  
Control Diet ◽  
High Fat ◽  
Pregnant Mothers

Abstract Objectives Nutritional status during intrauterine and/or early postnatal life has substantial influences on adult offspring health. However, evidence on the impact of high fat diet (HFD)-induced maternal obesity on regulation of fetal bone development is sparse. Thus, we investigated the effects of maternal obesity in rodent and human cells on epigenetic regulation of osteoblast differentiation. Methods First, female Sprague-Dawley rats were fed either a low-fat AIN-93G control diet or a high fat diet (HFD) (45% fat calories) for 10 wk starting at 6 wk of age. Lean (from control diet) and obese (from HFD) female rats were then time-impregnated (n = 6 per group) by control diet fed male rats. At gestational day 18.5 (E18.5), all fetuses were taken and embryonic osteogenic calvarial cells (EOCCs) were isolated. Second, human osteo-progenitors of mesenchymal stem cells were isolated from umbilical cord following delivery from pregnant mothers. Results We found epigenetic regulation of polycomb-regulated gene Ezh2 (Enhancer of zeste homolog 2) in embryonic rats from HFD obese rat dams. Increased enrichment of repressive histone mark H3K27me3 on the gene body of SATB2 (ChIP Seq analysis) was associated with aberrant differentiation of EOCCs to mature osteoblasts. Knocking down Ezh2 in EOCCs and ST2 cells increased SATB2 expression; on the other hand, Ezh2 overexpression in EOCCs and ST2 cells decreased SATB2 expression. These data were consistent with ChIP experimental results showing strong association between H3K27me3, Ezh2 and SATB2. Second, human mesenchymal stem cells (MSCs) from umbilical cord (UC) were isolated following delivery from obese/overweight (pre-pregnancy BMI ≥ 25 kg/m2) and control (pre-pregnancy BMI between 19–25 kg/m2) pregnant mothers. We found: 1) UC-MSCs from pregnant obese/overweight mothers showed increased Ezh2 expression and decreased SATB2 mRNA expression, which was concurrent lower osteoblastogenesis potential in EOCCs; 2) ChIP experiments using H3K27me3 IP (immune-precipitation) showed significant association between H3K27me3, Ezh2 and SATB2. Conclusions These findings indicate maternal HFD-induced obesity-associated decrease of fetal pre-osteoblastic cell differentiation is under epigenetic control through SATB2 expression. Funding Sources Supported by USDA-ARS Project.

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