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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncotarget
2017 ; 8
(32
): 53581-53601
Nephropedia Template TP
gab.com Text
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English Wikipedia
lncRNA H19 mediates BMP9-induced osteogenic differentiation of mesenchymal stem
cells (MSCs) through Notch signaling
#MMPMID28881833
Liao J
; Yu X
; Hu X
; Fan J
; Wang J
; Zhang Z
; Zhao C
; Zeng Z
; Shu Y
; Zhang R
; Yan S
; Li Y
; Zhang W
; Cui J
; Ma C
; Li L
; Yu Y
; Wu T
; Wu X
; Lei J
; Wang J
; Yang C
; Wu K
; Wu Y
; Tang J
; He BC
; Deng ZL
; Luu HH
; Haydon RC
; Reid RR
; Lee MJ
; Wolf JM
; Huang W
; He TC
Oncotarget
2017[Aug]; 8
(32
): 53581-53601
PMID28881833
show ga
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can undergo
self-renewal and differentiate into multiple lineages. Osteogenic differentiation
from MSCs is a well-orchestrated process and regulated by multiple signaling
pathways. We previously demonstrated that BMP9 is one of the most potent
osteogenic factors. However, molecular mechanism through which BMP9 governs
osteoblastic differentiation remains to be fully understood. Increasing evidence
indicates noncoding RNAs (ncRNAs) may play important regulatory roles in many
physiological and/or pathologic processes. In this study, we investigate the role
of lncRNA H19 in BMP9-regulated osteogenic differentiation of MSCs. We
demonstrated that H19 was sharply upregulated at the early stage of BMP9
stimulation of MSCs, followed by a rapid decease and gradual return to basal
level. This process was correlated with BMP9-induced expression of osteogenic
markers. Interestingly, either constitutive H19 expression or silencing H19
expression in MSCs significantly impaired BMP9-induced osteogenic differentiation
in vitro and in vivo, which was effectively rescued by the activation of Notch
signaling. Either constitutive H19 expression or silencing H19 expression led to
the increased expression of a group of miRNAs that are predicted to target Notch
ligands and receptors. Thus, these results indicate that lncRNA H19 functions as
an important mediator of BMP9 signaling by modulating Notch signaling-targeting
miRNAs. Our findings suggest that the well-coordinated biphasic expression of
lncRNA H19 may be essential in BMP9-induced osteogenic differentiation of MSCs,
and that dysregulated H19 expression may impair normal osteogenesis, leading to
pathogenic processes, such as bone tumor development.