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A Lox/CHOP-10 crosstalk governs osteogenic and adipogenic cell fate by MSCs.


ABSTRACT: Accelerated marrow adipogenesis has been associated with ageing and osteoporosis and is thought to be because of an imbalance between adipogenic and osteogenic differentiation of mesenchymal stem cell (MSCs). We have previously found that lysyl oxidase (Lox) inhibition disrupts BMP4-induced adipocytic lineage commitment and differentiation of MSCs. In this study, we found that lox inhibition dramatically up-regulates BMP4-induced expression of CCAAT/enhancer binding protein (C/EBP) homologous protein 10 (CHOP-10), which then promotes BMP4-induced osteogenesis of MSCs both in vitro and in vivo. Specifically, Lox inhibition or CHOP-10 up-regulation activated Wnt/?-catenin signalling to enhance BMP4-induced osteogenesis, with pro-adipogenic p38 MAPK and Smad signalling suppressed. Together, we demonstrate that Lox/CHOP-10 crosstalk regulates BMP4-induced osteogenic and adipogenic fate determination of MSCs, presenting a promising therapeutic target for osteoporosis and other bone diseases.

SUBMITTER: Jiang WY 

PROVIDER: S-EPMC6156357 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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A Lox/CHOP-10 crosstalk governs osteogenic and adipogenic cell fate by MSCs.

Jiang Wen-Yan WY   Xing Chun C   Wang Hong-Wei HW   Wang Wei W   Chen Su-Zhen SZ   Ning Liu-Fang LF   Xu Xu X   Tang Qi-Qun QQ   Huang Hai-Yan HY  

Journal of cellular and molecular medicine 20180725 10


Accelerated marrow adipogenesis has been associated with ageing and osteoporosis and is thought to be because of an imbalance between adipogenic and osteogenic differentiation of mesenchymal stem cell (MSCs). We have previously found that lysyl oxidase (Lox) inhibition disrupts BMP4-induced adipocytic lineage commitment and differentiation of MSCs. In this study, we found that lox inhibition dramatically up-regulates BMP4-induced expression of CCAAT/enhancer binding protein (C/EBP) homologous pr  ...[more]

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