PPARγ suppression inhibits adipogenesis but does not promote osteogenesis of human mesenchymal stem cells

Yu, Weihua; Li, Fugui; Chen, Xiaoyong; Li, Jiantao; Wu, Yanheng; Hu, Lihua; Zhen, Wang; Li, Panlong; Wang, Tao; Lahn, Bruce T.; Xiang, Andy Peng

doi:10.1016/j.biocel.2011.11.013

Cited by 62 publications

(55 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…45,46 Furthermore, knocking down the expression of C/EBPa prevents PPARg2 induction and adipogenesis in human marrow cells. 44 The expression profile during terminal adipogenic differentiation in human MSCs is also similar to that of 3T3-L1 preadipocytes, characterized by early expression of C/EBPb and -d and followed by C/EBPa and PPARg expression. 42 In addition, we have shown specific induction of PPARg2 in human marrow MPCs following addition of adipogenic differentiation media and the levels parallel C/EBPa.…”

Section: Mechanisms Of Enhanced Marrow Adipogenesis In Diabetesmentioning

confidence: 74%

“…For example, Yu and colleagues suggested that human marrow cells primarily express PPARg1 isoform upon differentiation with PPARg2 increases being noted at later time point, which is believed to be in contrast to murine cells. 44 PPARg2 isoform does appear to be the minor species, comprising only 15% of all PPARg expression within adipose tissue, although it has been shown to be the predominant isoform in regulating adipogenesis. 45,46 Furthermore, knocking down the expression of C/EBPa prevents PPARg2 induction and adipogenesis in human marrow cells.…”

Section: Mechanisms Of Enhanced Marrow Adipogenesis In Diabetesmentioning

confidence: 95%

See 1 more Smart Citation

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

Piccinin

Khan

2014

Adipocyte

View full text Add to dashboard Cite

Section: Mechanisms Of Enhanced Marrow Adipogenesis In Diabetesmentioning

confidence: 74%

Section: Mechanisms Of Enhanced Marrow Adipogenesis In Diabetesmentioning

confidence: 95%

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

Piccinin

Khan

2014

Adipocyte

View full text Add to dashboard Cite

“…Concomitantly, in vitro evidence from Yu and colleagues (23) showed reduced adipocyte differentiation in cultures of MSC treated with BADGE, although these investigators failed to provide evidence of altered osteoblastogenesis. Both the in vitro and in vivo data indicated that BADGE is an effective inhibitor of adipocyte differentiation and adipogenesis.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of PPARγ increases osteoblastogenesis and bone mass in male C57BL/6 mice

Duque

Vidal

et al. 2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Infiltration of bone marrow with fat is a prevalent feature in people with age-related bone loss and osteoporosis, which correlates inversely with bone formation and positively with high expression levels of peroxisomal proliferator-activated receptor gamma (PPARg). Inhibition of PPARg thus represents a potential therapeutic approach for age-related bone loss. In this study, we examined the effect of PPARg inhibition on bone in skeletally mature C57BL/6 male mice. Nine-month-old mice were treated with a PPARg antagonist, bisphenol-A-diglycidyl ether (BADGE), alone or in combination with active vitamin D (1,25[OH] 2 D 3 ) for 6 weeks. Micro-computed tomography and bone histomorphometry indicated that mice treated with either BADGE or BADGE þ 1,25(OH) 2 D 3 had significantly increased bone volume and improved bone quality compared with vehicle-treated mice. This phenotype occurred in the absence of alterations in osteoclast number. Furthermore, the BADGE þ 1,25(OH) 2 D 3 -treated mice exhibited higher levels of unmineralized osteoid. All of the treated groups showed a significant increase in circulating levels of bone formation markers without changes in bone resorption markers, while blood glucose, parathyroid hormone, and Ca þ remained normal. Furthermore, treatment with BADGE induced higher levels of expression of vitamin D receptor within the bone marrow. Overall, treated mice showed higher levels of osteoblastogenesis and bone formation concomitant with decreased marrow adiposity and ex vivo adipogenesis. Taken together, these observations demonstrate that pharmacological inhibition of PPARg may represent an effective anabolic therapy for osteoporosis in the near future. ß

show abstract

“…This suggests that the activation of the P2Y 13 R inhibits adipocyte differentiation and implies that the adipogenic stimulation stimulates the accumulation of ADP in the extracellular space, what we also observe. CEBP/b and PPARc1 are transcription factors that regulate the first steps of adipocyte differentiation [22,56]. The P2Y 13 R gene targeting does not modulate their mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

“…It is well-established that they are both involved in the differentiation of MSCs into adipocytes, but several studies support that PPARc2 is expressed later and more selectively in fat cell lineage. Moreover, PPARc2 is known to have a greater specificity to induce adipogenesis [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Role of the P2Y13 Receptor in the Differentiation of Bone Marrow Stromal Cells into Osteoblasts and Adipocytes

et al. 2013

View full text Add to dashboard Cite

Accumulating evidence indicates that extracellular nucleotides, signaling through purinergic receptors, play a significant role in bone remodeling. Mesenchymal stem cells (MSCs) express functional P2Y receptors whose expression level is regulated during osteoblast or adipocyte differentiation. P2Y 13 -deficient mice were previously shown to exhibit a decreased bone turnover associated with a reduction in the number of both osteoblasts and osteoclasts on the bone surfaces. We therefore examined whether P2Y 13 R activation was involved in the osteogenic differentiation of MSC. Our study demonstrated that ADP stimulation of P2Y 13 R 1/1 (but not P2Y 13 R -/-) adherent bone marrow stromal cells (BMSCs) increased significantly the formation of alkaline phosphatase-colony-forming units (CFU-ALP) as well as the expression of osteoblastic markers (osterix, alkaline phosphatase, and collagen I) involved in the maturation of preosteoblasts into osteoblasts. The number of CFU-ALP obtained from P2Y 13 R -/-BMSC and the level of osteoblastic gene expression after osteogenic stimulation were strongly reduced compared to those obtained in wild-type cell cultures. In contrast, when P2Y 13 R -/-BMSCs were incubated in an adipogenic medium, the number of adipocytes generated and the level of adipogenic gene expression (PPARc2 and Adipsin) were higher than those obtained in P2Y 13 R 1/1 MSC. Interestingly, we observed a significant increase of the number of bone marrow adipocytes in tibia of P2Y 13 R -/-mice. In conclusion, our findings indicate that the P2Y 13 R plays an important role in the balance of osteoblast and adipocyte terminal differentiation of bone marrow progenitors. Therefore, the P2Y 13 receptor can be considered as a new pharmacological target for the treatment of bone diseases like osteoporosis. STEM CELLS

show abstract

PPARγ suppression inhibits adipogenesis but does not promote osteogenesis of human mesenchymal stem cells

Cited by 62 publications

References 30 publications

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

Pathophysiological role of enhanced bone marrow adipogenesis in diabetic complications

Pharmacological inhibition of PPARγ increases osteoblastogenesis and bone mass in male C57BL/6 mice

Role of the P2Y13 Receptor in the Differentiation of Bone Marrow Stromal Cells into Osteoblasts and Adipocytes

Contact Info

Product

Resources

About