Thiazolidinediones and glucocorticoids synergistically induce differentiation of human adipose tissue stromal cells: Biochemical, cellular, and molecular analysis

Halvorsen, Yuan-Di C.; Bond, Arden L.; Sen, Abhik; Franklin, Dawn M.; Lea-Currie, Y. Renee; Sujkowski, Danuta; Ellis, Pamela N.; Wilkison, William O.; Gimble, Jeffrey M.

doi:10.1053/meta.2001.21690

Cited by 190 publications

(131 citation statements)

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“…Differentiation studies in 3T3-L1 cells have reported that the expression of mRNA for FABP4 is absent in undifferentiated cells, is detectable by day 3 of differentiation and then rapidly increases towards a steady state around day 8 (several 100-fold increase in gene expression), for up to 28 days. 20,22,27 Similar profiles of FABP4 gene expression have been observed during the differentiation of human marrow and adipose tissue stromal cells into adipocytes, 28,29 as well as during the differentiation of SGBS cells. 16 We specifically analysed the expression profile of FABP4 during the differentiation of SGBS cells to relate GIPR expression to a well-established molecular differentiation marker of adipogenesis.…”

Section: Discussionsupporting

confidence: 54%

Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model

et al. 2008

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Objective: To establish that human adipocytes express functional glucose-dependent insulinotropic peptide (GIP) receptors and in particular the regulation of GIP receptor (GIPR) expression in the context of the dynamic process of adipocyte differentiation. Design: A combination of semiquantitative real-time PCR and measurement of GIP-stimulated cAMP accumulation was used to establish the expression and functional coupling of GIPRs during in vitro differentiation of human Simpson-Golabi-Behmel syndrome (SGBS) preadipocytes. Results: Semiquantitative real-time PCR revealed that GIPR expression was substantially increased by day 4 of differentiation, reaching a maximum around 6-8 days (B200-fold increase above undifferentiated cells, n ¼ 2). We also analysed the expression of the adipocyte fatty acid binding protein (FABP4) to relate GIPR expression to a molecular differentiation marker of adipogenesis. FABP4 expression was barely detectable in undifferentiated cells. However, following exposure to adipogenic medium, FABP4 expression gradually increased, with a maximal expression level around 10 days (B1 600 000-fold increase above undifferentiated cells, n ¼ 2). Thus, the increases in GIPR mRNA during adipogenesis occur earlier than FABP4, suggesting that it might represent a gene expressed early in terminal differentiation and thus plays a role in fat droplet formation. A unit of 1 mM GIP failed to raise intracellular cAMP levels above basal levels in undifferentiated cells (n ¼ 3). In stark contrast, the 9-day differentiated cells produced a robust concentration-dependent increase in cAMP accumulation following stimulation with GIP, with an EC 50 value of 2.3 nM (n ¼ 3). The maximal response represented a 9-34-fold increase in cAMP accumulation above basal levels. Conclusions: This study demonstrates that GIPRs are expressed by human adipocytes, both GIPR mRNA and functional receptor expression being present in differentiated adipocytes but not in preadipocytes. Further investigation into the functional effects of GIP on differentiated SGBS cells could help towards understanding exactly how GIP regulates fat accumulation in human adipocytes.

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Section: Discussionsupporting

confidence: 54%

Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model

et al. 2008

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“…25,26 The SVcell pellet is suspended in omental preadipocyte medium (DMEM/F12, HEPES pH 7.4, FBS, biotin, pantothenate, insulin, dexamethasone and antibiotics) and plated in a culture flask for expansion. Preadipocytes are subcultured prior to reaching confluence and plated at a density of 6300 cells cm À2 for further expansion in preadipocyte media containing growth factors.…”

Section: Methodsmentioning

confidence: 99%

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue

et al. 2007

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Objective: Adiponectin is an adipokine produced by adipose tissue. The present studies examined the in vitro release of adiponectin by human omental adipose tissue explants as well as the mRNA content of freshly isolated non-fat cells and adipocytes plus cultured preadipocytes and adipocytes derived from omental fat. Results: The release of adiponectin was reduced while that of interleukin-8 (IL-8) was enhanced in tissue explants from morbidly obese women. The release of adiponectin was also reduced by one-third in explants from morbidly obese diabetic women while that of IL-8 was unaffected by diabetes. The release of adiponectin was enhanced by insulin and by inhibition of endogenous tumor necrosis factor (TNFa) using etancercept. Adiponectin was released in appreciable amounts by the undigested matrix obtained by collagenase digestion of adipose tissue. The release of adiponectin by non-fat cells (matrix þ SV cells) was comparable to that by the adipocytes derived from the same amount of tissue while the adiponectin mRNA content of the pooled matrix and SV cell fractions was 40% of that in intact tissue. The adiponectin mRNA content was 48-fold greater in isolated adipocytes than in non-fat cells derived from adipose tissue. In contrast, the amount of adiponectin mRNA in vitro differentiated omental adipocytes was 1 Â l0 6 -fold greater than that in cultured preadipocytes while that of leptin was 3 Â 10 4 -fold greater. Conclusion: Adiponectin mRNA is present in the non-fat cells of freshly isolated adipose tissue and release by the non-fat cells derived from a gram of adipose tissue is comparable to that by adipocytes isolated from the same amount of tissue. While leptin is only released by mature adipocytes, adiponectin is released by both the non-fat cells and the fat cells derived from human omental adipose tissue.

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“…The stromal-vascular fraction of cells is separated from the mature lipid-laden adipocytes by centrifugation. This fraction, which represents a heterogeneous population of cells, contains the ASCs [37,86]. A large number of ASCs can be harvested in this manner, with yields of approximately 250,000 cells per gram of tissue [3].…”

Section: Adipose Tissue As a Source Of Multipotent Adult Stem Cellsmentioning

confidence: 99%

2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering

Guilak

Estes

Diekman

et al. 2010

Clinical Orthopaedics &Amp; Related Research

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Background Cell-based therapies such as tissue engineering provide promising therapeutic possibilities to enhance the repair or regeneration of damaged or diseased tissues but are dependent on the availability and controlled manipulation of appropriate cell sources. Questions/purposes The goal of this study was to test the hypothesis that adult subcutaneous fat contains stem cells with multilineage potential and to determine the influence of specific soluble mediators and biomaterial scaffolds on their differentiation into musculoskeletal phenotypes. Methods We reviewed recent studies showing the stemlike characteristics and multipotency of adipose-derived stem cells (ASCs), and their potential application in cellbased therapies in orthopaedics.

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Thiazolidinediones and glucocorticoids synergistically induce differentiation of human adipose tissue stromal cells: Biochemical, cellular, and molecular analysis

Cited by 190 publications

References 0 publications

Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model

Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model

Regulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissue

2010 Nicolas Andry Award: Multipotent Adult Stem Cells from Adipose Tissue for Musculoskeletal Tissue Engineering

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