Differentiation‐dependent regulation of the cyclooxygenase cascade during adipogenesis suggests a complex role for prostaglandins

Xie, Yizhen; Kang, Xihai; Ackerman, William E.; Belury, Martha A.; Koster, C. H.; Rovin, Brad H.; Landon, Mark B.; Kniss, Douglas A.

doi:10.1111/j.1463-1326.2005.00472.x

Cited by 42 publications

(37 citation statements)

References 51 publications

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“…The PGE2 level was significantly lower in the presence of troglitazone when compared to the level in the absence of a PPARγ agonist. When exogenously added to hBM-MSC cultures, low nanomolar concentrations of PGE2 inhibited adipocyte differentiation (data not shown), as reported in those of murine pre-adipocytes (Reginato et al, 1998;Xie et al, 2006). Because hBM-MSCs constitutively express COX-1 and COX-2 (Arikawa et al, 2004), PGE 2 generated from hBM-MSCs may function as an intrinsic negative feedback regulator for the differentiation of hBM-MSCs.…”

Section: Discussionmentioning

confidence: 60%

“…The COX mRNA levels during adipocyte differentiation in hBM-MSCs were even up-regulated than that of the hBM-MSC control in our study. In contrast, gene transcriptions of COX-1 and COX-2 during adipocyte differentiation in murine pre-adipocyte systems have been reported unchanged or down-regulated (Yan et al, 2003;Xie et al, 2006). In this regard, COX gene expression patterns represent one of the major differences observed during adipocyte differentiation between hBM-MSCs and murine pre-adipocytes.…”

Section: Discussionmentioning

confidence: 83%

“…Prostaglandins play roles as autocrines and/or paracrines to regulate adipocyte differentiation and its function (Gregoire et al, 1998;Reginato et al, 1998;Xie et al, 2006). In this study, we evaluated the PGE2 levels in hBM-MSCs during adipocyte differentiation and analyzed the mRNA expressions of COXs, PGE2 synthases, and HPGD.…”

Section: Discussionmentioning

confidence: 99%

“…We found that the requirement of PPARγ activation for promoting adipocyte differentiation in hBM-MSCs may be associated with PPARγ-dependent up-regulation of the HPGD gene expression. In murine pre-adipocytes, adipogenic differentiation was followed by a significant reduction in PGE2 level (Yan et al, 2003;Tsuboi et al, 2004;Xie et Fig. 4.…”

Section: Discussionmentioning

confidence: 99%

“…PGE 2 levels in hBM-MSC culture did not correlate with gene expression of either COX-1 or COX-2 during adipocyte differentiation It has been reported that gene and protein expression of COXs is down-regulated during adipogenesis in murine 3T3-L1 cells (Yan et al, 2003;Xie et al, 2006). When we examined the expression profile of COX genes during adipocyte differentiation, surprisingly, mRNA levels of both COX-1 and COX-2 were significantly up-regulated upon stimulation of adipocyte differentiation in hBM-MSCs when compared to that of the control ( Fig.…”

Section: Pparγ Activation Decreased the Level Of Anti-adipogenic Pge mentioning

confidence: 99%

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15-Hydroxyprostaglandin Dehydrogenase Is Associated with the Troglitazone-Induced Promotion of Adipocyte Differentiation in Human Bone Marrow Mesenchymal Stem Cells

Noh¹,

Lee²

2010

Biomolecules and Therapeutics

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-Adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) is not as efficient as that in murine pre-adipocytes when induced by adipogenic agents including insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IDX condition). Therefore, the promotion of adipocyte differentiation in hBM-MSCs has been used as a cell culture model to evaluate insulin sensitivity for anti-diabetic drugs. In hBM-MSCs, PPARγ agonists or sulfonylurea anti-diabetic drugs have been added to IDX conditions to promote adipocyte differentiation. Here we show that troglitazone, a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, significantly reduced the levels of anti-adipogenic PGE 2 in IDX-conditioned hBM-MSC culture supernatants when compared to PGE2 levels in the absence of PPARγ agonist. However, there was no difference in the mRNA levels of cyclooxygenases (COXs) and the activities of COXs and prostaglandin synthases during adipocyte differentiation in hBM-MSCs with or without troglitazone. In hBM-MSCs, troglitazone significantly increased the mRNA level of 15-hydroxyprostaglandin dehydrogenase (HPGD) which can act to decrease PGE2 levels in culture. These results suggest that the role of PPARγ activation in promoting adipocyte differentiation in hBM-MSCs is to reduce anti-adipogenic PGE 2 levels through the up-regulation of HPGD expression.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Pparγ Activation Decreased the Level Of Anti-adipogenic Pge mentioning

confidence: 99%

See 3 more Smart Citations

15-Hydroxyprostaglandin Dehydrogenase Is Associated with the Troglitazone-Induced Promotion of Adipocyte Differentiation in Human Bone Marrow Mesenchymal Stem Cells

Noh¹,

Lee²

2010

Biomolecules and Therapeutics

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Current literature in diabetes

2006

Diabetes Metabolism Res

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author

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Endogenous synthesis of prostacyclin was positively regulated during the maturation phase of cultured adipocytes

et al. 2013

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Prostacyclin alternatively called prostaglandin (PG) I2 is an unstable metabolite synthesized by the arachidonate cyclooxygenase pathway. Earlier studies have suggested that prostacyclin analogues can act as a potent effector of adipose differentiation. However, biosynthesis of PGI2 has not been determined comprehensively at different life stages of adipocytes. PGI2 is rapidly hydrolyzed to the stable product, 6-keto-PGF1α, in biological fluids. Therefore, the generation of PGI2 can be quantified as the amount of 6-keto-PGF1α. In this study, we attempted to develop a solid-phase enzyme-linked immunosorbent assay (ELISA) using a mouse antiserum specific for 6-keto-PGF1α. According to the typical calibration curve of our ELISA, 6-keto-PGF1α can be quantified from 0.8 pg to 7.7 ng in an assay. The evaluation of our ELISA revealed the higher specificity of our antiserum without the cross-reaction with other related prostanoids while it exhibited only the cross-reaction of 1.5 % with PGF2α. The resulting ELISA was applied to the quantification of 6-keto-PGF1α generated endogenously by cultured 3T3-L1 cells at different stages. The cultured cells showed the highest capability to generate 6-keto-PGF1α during the maturation phase of 4-6 days, which was consistent with the coordinated changes in the gene expression of PGI synthase and the IP receptor for PGI2. Following these events, the accumulation of fats was continuously promoted up to 14 days. Thus, our immunological assay specific for 6-keto-PGF1α is useful for monitoring the endogenous levels of the unstable parent PGI2 at different life stages of adipogenesis and for further studies on the potential association with the up-regulation of adipogenesis in cultured adipocytes.

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Differentiation‐dependent regulation of the cyclooxygenase cascade during adipogenesis suggests a complex role for prostaglandins

Abstract: Regulation of PG formation and COX-2 expression in 3T3-L1 cells is differentiation-dependent and involves changes in the levels of gene expression of the individual isoforms as well as redistribution of the enzymes within cellular compartments.

Cited by 42 publications

References 51 publications

15-Hydroxyprostaglandin Dehydrogenase Is Associated with the Troglitazone-Induced Promotion of Adipocyte Differentiation in Human Bone Marrow Mesenchymal Stem Cells

15-Hydroxyprostaglandin Dehydrogenase Is Associated with the Troglitazone-Induced Promotion of Adipocyte Differentiation in Human Bone Marrow Mesenchymal Stem Cells

Current literature in diabetes

Endogenous synthesis of prostacyclin was positively regulated during the maturation phase of cultured adipocytes

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