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Adipogenic Lineages (adipogenic + lineage)

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Life Sciences	75%

Selected Abstracts

Thiazolidinedione treatment and constitutive-PPAR, activation induces ectopic adipogenesis and promotes age-related thymic involution

AGING CELL, Issue 4 2010
Yun-Hee Youm
Summary Age-related thymic involution is characterized by reduction in T cell production together with ectopic adipocyte development within the hematopoietic and thymic niches. Peroxisome proliferator-activated receptor gamma (PPAR,) is required for adipocyte development, glucose homeostasis and is a target for several insulin-sensitizing drugs. Our prior studies showed that age-related elevation of PPAR, expression in thymic stromal cells is associated with thymic involution. Here, using clinically relevant pharmacological and genetic manipulations in mouse models, we provide evidence that activation of PPAR, leads to reduction in thymopoiesis. Treatment of aged mice with antihyperglycemic PPAR,-ligand class of thiazolidinedione drug, rosiglitazone caused robust thymic expression of classical pro-adipogenic transcripts. Rosiglitazone reduced thymic cellularity, lowered the naïve T cell number and T cell receptor excision circles (TRECs) indicative of compromised thymopoiesis. To directly investigate whether PPAR, activation induces thymic involution, we created transgenic mice with constitutive-active PPAR, (CA-PPARg) fusion protein in cells of adipogenic lineage. Importantly, CA-PPAR, transgene was expressed in thymus and in fibroblast-specific protein-1/S100A4 (FSP1+) cells, a marker of secondary mesenchymal cells. The CAPPAR, fusion protein mimicked the liganded PPAR, receptor and the transgenic mice displayed increased ectopic thymic adipogenesis and reduced thymopoiesis. Furthermore, the reduction in thymopoiesis in CA-PPAR, mice was associated with higher bone marrow adiposity and lower hematopoietic stem cell progenitor pool. Consistent with lower thymic output, CAPPAR, transgenic mice had restricted T cell receptor repertoire diversity. Collectively, our data suggest that activation of PPAR, accelerates thymic aging and thymus-specific PPAR, antagonist may forestall age-related decline in T cell diversity. [source]

Plasticity of clonal populations of dedifferentiated adult human articular chondrocytes

ARTHRITIS & RHEUMATISM, Issue 5 2003
Andrea Barbero
Objective To investigate whether adult human articular chondrocytes (AHACs), dedifferentiated by monolayer expansion, can differentiate toward diverse mesenchymal lineages and, if so, whether this ability is regulated by growth factors during monolayer expansion. Methods AHACs were expanded as multiclonal or clonal populations in medium without (control) or with factors enhancing cell dedifferentiation (transforming growth factor ,1, fibroblast growth factor 2, and platelet-derived growth factor type BB [TFP]). Cells were then cultured under conditions promoting chondrogenic, osteogenic, or adipogenic differentiation, and the acquired phenotypes were assessed histologically, biochemically, and by real-time reverse transcriptase,polymerase chain reaction. Results Multiclonal populations of both control- and TFP-expanded AHACs differentiated toward the chondrogenic, osteogenic, and adipogenic lineages. Compared with control-expanded AHACs, TFP-expanded cells displayed enhanced chondrogenic differentiation capacity (2.4-fold higher glycosaminoglycan/DNA content and 2,500-fold higher up-regulation of type II collagen) and osteogenic differentiation capacity (9.4-fold higher increase in alkaline phosphatase activity and 12.4-fold higher up-regulation of bone sialoprotein), but reduced formation of adipocytes (5.2-fold lower oil red O,positive cells/area). Clonal populations of AHACs could be efficiently expanded in TFP, but not in control medium. Most TFP-expanded clones were able to redifferentiate only into chondrocytes (7 of 20) or were unable to differentiate (6 of 20). However, some clones (2 of 20) differentiated toward all of the lineages investigated, thus displaying characteristics of mesenchymal progenitor cells. Conclusion Dedifferentiated AHACs exhibit differentiation plasticity, which is modulated by growth factors used during monolayer expansion and is highly heterogeneous across different clones. Clonal culture of AHACs in the presence of regulatory molecules could lead to the identification of AHAC subpopulations with enhanced cartilage repair capacity. [source]

EMF acts on rat bone marrow mesenchymal stem cells to promote differentiation to osteoblasts and to inhibit differentiation to adipocytes

BIOELECTROMAGNETICS, Issue 4 2010
Yong Yang
Abstract The use of electromagnetic fields (EMFs) to treat nonunion fractures developed from observations in the mid-1900s. Whether EMF directly regulates the bone marrow mesenchymal stem cells (MSCs), differentiating into osteoblasts or adipocytes, remains unknown. In the present study, we investigated the roles of sinusoidal EMF of 15,Hz, 1,mT in differentiation along these separate lineages using rat bone marrow MSCs. Our results showed that EMF promoted osteogenic differentiation of the stem cells and concurrently inhibited adipocyte formation. EMF increased alkaline phosphatase (ALP) activity and mineralized nodule formation, and stimulated osteoblast-specific mRNA expression of RUNX2, ALP, BMP2, DLX5, and BSP. In contrast, EMF decreased adipogenesis and inhibited adipocyte-specific mRNA expression of adipsin, AP-2, and PPAR,2, and also inhibited protein expression of PPAR,2. These observations suggest that commitment of MSCs into osteogenic or adipogenic lineages is influenced by EMF. Bioelectromagnetics 31:277,285, 2010. © 2009 Wiley-Liss, Inc. [source]

Cell proliferation of human bone marrow mesenchymal stem cells on biodegradable microcarriers enhances in vitro differentiation potential

CELL PROLIFERATION, Issue 5 2010
L.-Y. Sun
Objectives:, For reasons of provision of highly-specific surface area and three-dimensional culture, microcarrier culture (MC) has garnered great interest for its potential to expand anchorage-dependent stem cells. This study utilizes MC for in vitro expansion of human bone marrow mesenchymal stem cells (BMMSCs) and analyses its effects on BMMSC proliferation and differentiation. Materials and methods:, Effects of semi-continuous MC compared to control plate culture (PC) and serial bead-to-bead transfer MC (MC bead-T) on human BMMSCs were investigated. Cell population growth kinetics, cell phenotypes and differentiation potential of cells were assayed. Results:, Maximum cell density and overall fold increase in cell population growth were similar between PCs and MCs with similar starting conditions, but lag period of BMMSC growth differed substantially between the two; moreover, MC cells exhibited reduced granularity and higher CXCR4 expression. Differentiation of BMMSCs into osteogenic and adipogenic lineages was enhanced after 3 days in MC. However, MC bead-T resulted in changes in cell granularity and lower osteogenic and adipogenic differentiation potential. Conclusions:, In comparison to PC, MC supported expansion of BMMSCs in an up-scalable three-dimensional culture system using a semi-continuous process, increasing potential for stem cell homing ability and osteogenic and adipogenic differentiation. [source]