CCAAT/Enhancer Binding Protein β Abrogates Retinoic Acid-Induced Osteoblast Differentiation via Repression of Runx2 Transcription

Wiper‐Bergeron, Nadine; St-Louis, Catherine; Lee, Jonathan M.

doi:10.1210/me.2006-0452

Cited by 34 publications

(52 citation statements)

References 45 publications

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“…Studies from the Wahli laboratory (59) have shown inhibition of peroxisome proliferator-activated receptor ␤expression by C/EBP␤ and its association with histone deacetylase in the control of differentiation and proliferation of keratinocytes. It can also bind directly to the C/EBP element on the osteoblast-specific Runx2 promoter independent of deacetylase activity to repress gene expression, resulting in an inhibition of retinoic acid-induced osteoblast differentiation (60). In our studies, C/EBP␤ at low concentrations enhances calcitonin-induced 1␣(OH)ase transcription, but at high concentrations repression of 1␣(OH)ase transcription was observed.…”

Section: Discussionmentioning

confidence: 45%

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Zhong

Armbrecht

Christakos

2009

Journal of Biological Chemistry

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Although parathyroid hormone (PTH) induces 25-hydroxyvitamin D 3 (25(OH)D 3 ) 1␣-hydroxylase (1␣(OH)ase) underhypocalcemic conditions, previous studies showed that calcitonin, not PTH, has an important role in the maintenance of serum 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) under normocalcemic conditions. In this study we report that 1␣(OH)ase transcription is strongly induced by calcitonin in kidney cells and indicate mechanisms that underlie this regulation. The transcription factor C/EBP␤ is up-regulated by calcitonin in kidney cells and results in a significant enhancement of calcitonin induction of 1␣(OH)ase transcription and protein expression. Mutation constructs of the 1␣(OH)ase promoter demonstrate the importance of the C/EBP␤ binding site at ؊79/؊73 for activation of the 1␣(OH)ase promoter by calcitonin. The SWI/SNF chromatin remodeling complex was found to cooperate with calcitonin in the regulation of 1␣(OH)ase. Chromatin immunoprecipitation analysis showed that calcitonin recruits C/EBP␤ to the 1␣(OH)ase promoter, and Re-chromatin immunoprecipitation analysis (sequential chromatin immunoprecipitations using different antibodies) showed that C/EBP␤ and BRG1, an ATPase that is a component of the SWI/SNF complex, bind simultaneously to the 1␣(OH)ase promoter. These findings are the first to address the dynamics between calcitonin, C/EBP␤, and SWI/SNF in the regulation of 1␣(OH)ase and provide a mechanism, for the first time, for calcitonin induction of 1␣(OH)ase. Because plasma calcitonin as well as 1,25(OH) 2 D 3 have been reported to be increased during pregnancy and lactation and in early development, these findings suggest a mechanism that may account, at least in part, for the increase in plasma 1,25(OH) 2 D 3 during these times of increased calcium requirement.Vitamin D is a principal factor required for maintaining normal calcium homeostasis (1). The active form of vitamin D,3 is generated by two successive hydroxylations; 25-hydroxylation in the liver and 1␣-hydroxylation in the kidney (1-3). Inactivating mutations in the 25-hydroxvitamin D 3 1␣-hydroxylase (1␣(OH)ase) gene result in vitamin D dependent rickets type I despite normal intake of vitamin D, indicating the importance of the 1␣(OH)ase enzyme (4, 5). Elevated parathyroid hormone (PTH) resulting from hypocalcemia is a primary signal mediating the renal synthesis of 1,25(OH) 2 D 3 (6). PTH stimulates 1␣(OH)ase transcription, resulting in increased 1,25(OH) 2 D 3 synthesis (7-9). However, under normocalcemic conditions, PTH fails to stimulate 1␣(OH)ase expression (10). Previous studies showed that calcitonin can enhance renal conversion of 25(OH)D 3 to 1,25(OH) 2 D 3 and that calcitonin, not PTH, is the major regulator of 1␣(OH)ase in the normocalcemic state (10 -13). In early development and during pregnancy and lactation calcitonin levels are increased under normocalcemic conditions and correlated to an increase in serum 1,25(OH) 2 D 3 levels (14 -17). The stimulation of 1,25(OH) 2 D 3 under normocalcemic conditions by calcitonin m...

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Section: Discussionmentioning

confidence: 45%

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Zhong

Armbrecht

Christakos

2009

Journal of Biological Chemistry

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“…The role of RA in osteoblastogenesis has been studied extensively in vitro and it has been shown to both promote and inhibit differentiation, as well as to drive bone matrix synthesis (Ahmed et al, 2000;Benayahu et al, 1994;Choong et al, 1993;Manji et al, 1998;Ohishi et al, 1995;Song et al, 2005;Wiper-Bergeron et al, 2007). Although variation between cell lines, the markers tested and experimental regimes might offer an explanation for these differing results, a clear consensus as to the role of RA has not emerged.…”

Section: Ra Signalling Is Required For Adipocyte Differentiation In Vivomentioning

confidence: 99%

Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways

Kelsh

Croucher

et al. 2010

Development

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SUMMARYAlthough the regulation of osteoblast and adipocyte differentiation from mesenchymal stem cells has been studied for some time, very little is known about what regulates their appearance in discrete regions of the embryo. Here we show that, as in other vertebrates, zebrafish osteoblasts and adipocytes originate in part from cephalic neural crest (CNC) precursors. We investigated the roles that the retinoic acid (RA) and Peroxisome proliferator-activated receptor gamma (Pparg) pathways play in vivo and found that both pathways act on CNC to direct adipocyte differentiation at the expense of osteoblast formation. In addition, we identify two distinct roles for RA in the osteoblast lineage: an early role in blocking the recruitment of osteoblasts and a later role in mature osteoblasts to promote bone matrix synthesis. These findings might help to increase our understanding of skeletal and obesityrelated diseases and aid in the development of stem cell-based regenerative therapies.KEY WORDS: Adipocyte, Osteoprogenitor, Osteoblast, Osteoblastogenesis, All trans retinoic acid, Bone, Cephalic neural crest, osterix (sp7), tcf7, Mesenchymal stem cell, Adipoprogenitor, Peroxisome proliferator-activated receptor gamma (Pparg), CCAAT/enhancer binding protein alpha (Cebpa), Runt-related transcription factor 2 (Runx2; Core binding factor a1), Zebrafish

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“…Initially discovered as a regulator of IL-6 expression, C/EBP␤ has been implicated in numerous differentiation processes including adipogenesis, osteoblastogenesis, mammary gland development, and female fertility (7)(8)(9)(10)(11). Cebpb is an intronless gene that produces a single mRNA from a single promoter (12).…”

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confidence: 99%

Mdm2 Promotes Myogenesis through the Ubiquitination and Degradation of CCAAT/Enhancer-binding Protein β

Lala-Tabbert

Lee

et al. 2015

Journal of Biological Chemistry

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Background: CCAAT/Enhancer-binding Protein ␤ (C/EBP␤) inhibits differentiation of muscle satellite cells and is rapidly down-regulated in early myogenesis. Results: The E3 ubiquitin ligase Mouse double minute 2 homolog (Mdm2) targets C/EBP␤ for degradation thereby promoting entry into myogenesis. Conclusion: Mdm2 expression is necessary for entry into myogenesis. Significance: Establishes a new role for Mdm2 in cellular differentiation.

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CCAAT/Enhancer Binding Protein β Abrogates Retinoic Acid-Induced Osteoblast Differentiation via Repression of Runx2 Transcription

Cited by 34 publications

References 45 publications

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Calcitonin, a Regulator of the 25-Hydroxyvitamin D3 1α-Hydroxylase Gene

Regulation of neural crest cell fate by the retinoic acid and Pparg signalling pathways

Mdm2 Promotes Myogenesis through the Ubiquitination and Degradation of CCAAT/Enhancer-binding Protein β

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