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Bone marrow adipocytes

Antonella Conforti, Nadia Starc, Simone Biagini, Luigi Tomao, Angela Pitisci, Mattia Algeri, Pietro Sirleto, Antonio Novelli, Giulia Grisendi, Olivia Candini, Cintia Carella, Massimo Dominici, Franco Locatelli, Maria Ester Bernardo
The risk of malignant transformation of ex-vivo expanded human mesenchymal stromal cells (huMSCs) has been debated in the last years; however, the biosafety of these cells after exposure to supramaximal physical and chemical stress has never been systematically investigated.We established an experimental in vitro model to induce supramaximal physical (ionizing radiation, IR) and chemical (starvation) stress on ex-vivo expanded bone marrow (BM)-derived huMSCs and investigated their propensity to undergo malignant transformation...
October 15, 2016: Oncotarget
Emma V Morris, Claire M Edwards
Adipocytes are a significant component of the bone marrow microenvironment. Although bone marrow adipocytes were first identified more than 100 years ago, it is only in recent years that an understanding of their complex physiological role is emerging. Bone marrow adipocytes act as local regulators of skeletal biology and homeostasis, with recent studies suggesting that marrow adipose tissue is metabolically active, and can function as an endocrine organ. As such, bone marrow adipocytes have the potential to interact with tumour cells, influencing both tumour growth and bone disease...
September 2016: Journal of Bone Oncology
Guanwu Li, Zheng Xu, Lingmi Hou, Xuefeng Li, Xin Li, Wei Yuan, Maki Polat, Shixin Chang
Bisphenol A diglycidyl ether (BADGE), a PPARγ2 antagonist, has been shown to inhibit marrow adipogenesis and promotes bone formation in intact animals. We investigated the impact of BADGE on a new and more clinically relevant physiological model, the ovariectomized (OVX) rat model. Forty female Wistar rats were divided into four treatment groups (n=10/group): sham+vehicle, sham+BADGE, OVX+vehicle and OVX+BADGE for 12 weeks. Postmortem analyses included MRI, micro-CT, serological test, histomorphometry, biomechanical tests, RT-PCR and western blot...
October 18, 2016: American Journal of Physiology. Endocrinology and Metabolism
Simone Vargas da Silva, Mariana Renovato-Martins, Cristiane Ribeiro-Pereira, Marta Citelli, Christina Barja-Fidalgo
OBJECTIVE: To investigate the role of obesity on the bone marrow microenvironment and evaluate its possible impact on the adipogenic potential of mesenchymal stem cells (MSC). METHODS: C57BL/6 male mice were fed with a high-fat diet (HFD) for 10 weeks. Femurs and tibiae were collected, and bone marrow mesenchymal stem cells (BM-MSC) were isolated and analyzed for proliferative potential, immunophenotype, and expression of adipogenesis markers. Their capacity to produce extracellular matrix proteins and proinflammatory cytokines in vitro was also evaluated...
October 18, 2016: Obesity
Younho Han, Chae Yul Kim, Heesun Cheong, Kwang Youl Lee
Osterix is a novel bone-related transcription factor involved in osteoblast differentiation, and bone maturation. Because a reciprocal relationship exists between adipocyte and osteoblast differentiation of bone marrow derived mesenchymal stem cells, we hypothesized that Osterix might have a role in adipogenesis. Ablation of Osterix enhanced adipogenesis in 3T3-L1 cells, whereas overexpression suppressed this process and inhibited the expression of adipogenic markers including CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ)...
October 18, 2016: Scientific Reports
Shanmugam Muruganandan, Rajgopal Govindarajan, Nichole M McMullen, Christopher J Sinal
Bone remodelling is a dynamic process requiring the coordinated action of formative (osteoblast) and resorptive (osteoclast) cell populations. An imbalance of the development and function of these cell types underlies several chronic bone loss disorders such as osteoporosis. Increased bone marrow adipocyte numbers commonly occur with bone loss disorders and numerous studies have documented an inverse relationship between bone marrow fat and bone formation. Osteoblasts and adipocytes derive in a competitive fashion from a common mesenchymal stem cell (MSC) precursor...
October 12, 2016: Stem Cells
Winifred Broekman, Helene Roelofs, Maria C Zarcone, Christian Taube, Jan Stolk, Pieter S Hiemstra
Autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) are evaluated for clinical use in chronic obstructive pulmonary disease (COPD) patients, but it is unclear whether COPD affects BM-MSCs. To investigate this, BM-MSCs from nine COPD patients and nine non-COPD age-matched controls were compared with regard to immunophenotype, growth and differentiation potential, and migration capacity. Other functional assays included the response to pro-inflammatory stimuli and inducers of the nuclear factor (erythroid derived 2)-like 2 antioxidant response element (Nrf2-ARE) pathway, and effects on NCI-H292 airway epithelial cells...
April 2016: ERJ Open Research
Laura Frese, Petra E Dijkman, Simon P Hoerstrup
In regenerative medicine, adult stem cells are the most promising cell types for cell-based therapies. As a new source for multipotent stem cells, human adipose tissue has been introduced. These so called adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative therapies. Their main advantage over mesenchymal stem cells derived from other sources, e.g. from bone marrow, is that they can be easily and repeatable harvested using minimally invasive techniques with low morbidity...
July 2016: Transfusion Medicine and Hemotherapy
Richard J Sulston, Brian S Learman, Bofeng Zhang, Erica L Scheller, Sebastian D Parlee, Becky R Simon, Hiroyuki Mori, Adam J Bree, Robert J Wallace, Venkatesh Krishnan, Ormond A MacDougald, William P Cawthorn
BACKGROUND: Bone marrow adipose tissue (MAT) contributes to increased circulating adiponectin, an insulin-sensitizing hormone, during caloric restriction (CR), but whether this occurs in other contexts remains unknown. The antidiabetic thiazolidinediones (TZDs) also promote MAT expansion and hyperadiponectinemia, even without increasing adiponectin expression in white adipose tissue (WAT). OBJECTIVES: To test the hypothesis that MAT expansion contributes to TZD-associated hyperadiponectinemia, we investigated the effects of rosiglitazone, a prototypical TZD, in wild-type (WT) or Ocn-Wnt10b mice...
2016: Frontiers in Endocrinology
Michaela Tencerova, Moustapha Kassem
Bone marrow (BM) microenvironment represents an important compartment of bone that regulates bone homeostasis and the balance between bone formation and bone resorption depending on the physiological needs of the organism. Abnormalities of BM microenvironmental dynamics can lead to metabolic bone diseases. BM stromal cells (also known as skeletal or mesenchymal stem cells) [bone marrow stromal stem cell (BMSC)] are multipotent stem cells located within BM stroma and give rise to osteoblasts and adipocytes. However, cellular and molecular mechanisms of BMSC lineage commitment to adipocytic lineage and regulation of BM adipocyte formation are not fully understood...
2016: Frontiers in Endocrinology
Olfa Ghali, Nathalie Al Rassy, Pierre Hardouin, Christophe Chauveau
Elevated bone marrow adiposity (BMA) is defined as an increase in the proportion of the bone marrow (BM) cavity volume occupied by adipocytes. This can be caused by an increase in the size and/or number of adipocytes. BMA increases with age in a bone-site-specific manner. This increase may be linked to certain pathophysiological situations. Osteoporosis or compromised bone quality is frequently associated with high BMA. The involvement of BM adipocytes in bone loss may be due to commitment of mesenchymal stem cells to the adipogenic pathway rather than the osteogenic pathway...
2016: Frontiers in Endocrinology
Sang-Gyu Lee, Kishore Gangangari, Teja Muralidhar Kalidindi, Blesida Punzalan, Steven M Larson, Naga Vara Kishore Pillarsetty
INTRODUCTION: Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [(18)F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow...
August 27, 2016: Nuclear Medicine and Biology
Lance A Stechschulte, Chunxi Ge, Terry D Hinds, Edwin R Sanchez, Renny T Franceschi, Beata Lecka-Czernik
Peroxisome proliferator-activated receptor gamma (PPARγ) and runt-related transcription factor 2 (RUNX2) are key regulators of mesenchymal stem cell (MSC) differentiation toward adipocytes and osteoblasts, respectively. Post-translational modifications of these factors determine their activities. Dephosphorylation of PPARγ at Serine 112 (S112) is required for its adipocytic activity, whereas phosphorylation of RUNX2 at Serine 319 (S319) promotes its osteoblastic activity. Here we show that protein phosphatase 5 (PP5) reciprocally regulates each receptor by targeting each serine...
September 29, 2016: Journal of Biological Chemistry
Yaqin Zhang, Hongliang Mei, Xiaoai Chang, Fang Chen, Yunxia Zhu, Xiao Han
The proinflammatory profile of M1 macrophage accumulation in adipose tissue is a central event leading to the metabolic complications of obesity. However, the mechanisms by which M1 macrophages are enriched in adipose tissue during weight gain remain incompletely understood. Here, we investigated the effects of adipocyte-derived microvesicles (ADM) on modulating macrophage phenotype in mice and explored the involved molecular signaling pathways. We found that, compared with ADM from lean mice (SD ADM), ADM from obese mice (HFD ADM) significantly enhanced M1 marker expression...
September 25, 2016: Journal of Molecular Cell Biology
Xiang Chen, Chunyu Wang, Kun Zhang, Ying Xie, Xiao Ji, Hui Huang, Xijie Yu
Growing evidence argues for a relationship between lipid and bone metabolisms with inconsistent conclusions. Sphingosine-1-phosphate (S1P) has been recognized as a suitable candidate for possible link between lipid metabolism and bone metabolism. This study was designed to investigate the effects of hyperlipidemia on bone metabolism using diet-induced and genetic-induced hyperlipidemia animal models and to explore whether S1P is involved. Wild-type mice and low-density lipoprotein receptor gene deficient (LDLR(-/-)) mice at age of 8weeks were placed on either control diet or high-fat diet (HFD) for 12weeks...
September 23, 2016: Bone
Timothy N Trotter, Justin T Gibson, Tshering Lama Sherpa, Pramod S Gowda, Deniz Peker, Yang Yang
Multiple myeloma (MM) cells reside in the bone marrow microenvironment and form complicated interactions with nonneoplastic, resident stromal cells. We previously found that aggressive MM cells shift osteoblast progenitors toward adipogenesis. In addition, adipocytes are among the most common cell types in the adult skeleton; both mature adipocytes and preadipocytes serve as endocrine cells that secrete a number of soluble molecules into the microenvironment. Therefore, we used a combination of in vivo and in vitro methods to test the hypothesis that an increase in adipocyte lineage cells feeds back to promote MM progression...
September 17, 2016: American Journal of Pathology
Abhishek Chandra, Tiao Lin, Tiffany Young, Wei Tong, Xiaoyuan Ma, Wei-Ju Tseng, Ina Kramer, Michaela Kneissel, Michael A Levine, Yejia Zhang, Keith Cengel, X Sherry Liu, Ling Qin
Focal radiotherapy is frequently associated with skeletal damage within the radiation field. Our previous in vitro study showed that activation of Wnt/β-catenin pathway can overcome radiation-induced DNA damage and apoptosis of osteoblastic cells. Neutralization of circulating Sclerostin with a monoclonal antibody (Scl-Ab) is an innovative approach for treating osteoporosis by enhancing Wnt/β-catenin signaling in bone. Together with the fact that focal radiation increases Sclerostin amount in bone, we sought to determine whether weekly treatment with Scl-Ab would prevent focal radiotherapy-induced osteoporosis in mice...
September 16, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Flavia Román, Carla Urra, Omar Porras, Ana María Pino, Clifford J Rosen, Juan Pablo Rodríguez
Oxidative stress (OS) derived from an increase in intracellular reactive oxygen species (ROS) is a major determinant of aging and lifespan. It has also been associated with several age-related disorders, like postmenopausal osteoporosis of Mesenchymal stem cells (MSCs). MSCs are the common precursors for osteoblasts and adipocytes; appropriate commitment and differentiation of MSCs into a specific phenotype is modulated, among other factors, by ROS balance. MSCs have shown more resistance to ROS than differentiated cells, and their redox status depends on complex and abundant anti-oxidant mechanisms...
September 15, 2016: Journal of Cellular Biochemistry
Akiko Takikawa, Arshad Mahmood, Allah Nawaz, Tomonobu Kado, Keisuke Okabe, Seiji Yamamoto, Aminuddin Arif, Satoko Senda, Koichi Tsuneyama, Masashi Ikutani, Yasuharu Watanabe, Yoshiko Igarashi, Yoshinori Nagai, Kiyoshi Takatsu, Keiichi Koizumi, Johji Imura, Nobuhito Goda, Masakiyo Sasahara, Michihiro Matsumoto, Kumiko Saeki, Takashi Nakagawa, Shiho Fujisaka, Isao Usui, Kazuyuki Tobe
Adipose tissue hypoxia is an important feature of pathological adipose tissue expansion. Hypoxia-inducible factor-1α (HIF-1α) in adipocytes reportedly induces oxidative stress and fibrosis, rather than neoangiogenesis via VEGF-A. We previously reported that macrophages in crown-like structures (CLSs) are both hypoxic and inflammatory. In the present study, we examined how macrophage HIF-1α is involved in high-fat diet (HFD)-induced inflammation, neovascularization, hypoxia, and insulin resistance using mice with myeloid cell-specific HIF-1α deletion fed an HFD...
September 13, 2016: Diabetes
Mikael Rydén
In the last decade, results in both animal models and humans have demonstrated that white adipocytes are generated over the entire life-span. This adds to the plasticity of adipose tissue and alterations in adipocyte turnover are linked to metabolic dysfunction. Adipocytes are derived from precursors present primarily in the perivascular areas of adipose tissue but their precise origin remains unclear. The multipotent differentiation capacity of bone marrow-derived cells (BMDC) has prompted the suggestion that BMDC may contribute to different cell tissue pools, including adipocytes...
July 2016: Adipocyte
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