Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24867947
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2014 ; 289
(29
): 20120-8
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Epigenetic modifications and canonical wingless/int-1 class (WNT) signaling
enable trans-differentiation of nonosteogenic cells into osteoblasts
#MMPMID24867947
Cho YD
; Yoon WJ
; Kim WJ
; Woo KM
; Baek JH
; Lee G
; Ku Y
; van Wijnen AJ
; Ryoo HM
J Biol Chem
2014[Jul]; 289
(29
): 20120-8
PMID24867947
show ga
Mesenchymal cells alter and retain their phenotype during skeletal development
through activation or suppression of signaling pathways. For example, we have
shown that Wnt3a only stimulates osteoblast differentiation in cells with
intrinsic osteogenic potential (e.g. MC3T3-E1 pre-osteoblasts) and not in fat
cell precursors or fibroblasts (3T3-L1 pre-adipocytes or NIH3T3 fibroblasts,
respectively). Wnt3a promotes osteogenesis in part by stimulating autocrine
production of the osteoinductive ligand Bmp2. Here, we show that the promoter
regions of the genes for Bmp2 and the osteoblast marker Alp are epigenetically
locked to prevent their expression in nonosteogenic cells. Both genes have
conserved CpG islands that exhibit increased CpG methylation, as well as
decreased acetylation and increased methylation of histone H3 lysine 9 (H3-K9)
specifically in nonosteogenic cells. Treatment of pre-adipocytes or fibroblasts
with the CpG-demethylating agent 5'-aza-2'-deoxycytidine or the histone
deacetylase inhibitor trichostatin-A renders Bmp2 and Alp responsive to Wnt3a.
Hence, drug-induced epigenetic activation of Bmp2 gene expression contributes to
Wnt3a-mediated direct trans-differentiation of pre-adipocytes or fibroblasts into
osteoblasts. We propose that direct conversion of nonosteogenic cells into
osteoblastic cell types without inducing pluripotency may improve prospects for
novel epigenetic therapies to treat skeletal afflictions.
|*Epigenesis, Genetic
[MESH]
|*Wnt Signaling Pathway
[MESH]
|3T3 Cells
[MESH]
|3T3-L1 Cells
[MESH]
|Adipocytes/cytology/metabolism
[MESH]
|Alkaline Phosphatase/genetics/metabolism
[MESH]
|Animals
[MESH]
|Bone Morphogenetic Protein 2/*genetics/*metabolism
[MESH]