Open AccessA Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs
Author(s) -
Jiang Wenyan,
Xing Chun,
Wang Hongwei,
Wang Wei,
Chen Suzhen,
Ning Liufang,
Xu Xu,
Tang Qiqun,
Huang Haiyan
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13798
Subject(s) - adipogenesis , mesenchymal stem cell , microbiology and biotechnology , chop , wnt signaling pathway , lysyl oxidase , chemistry , crosstalk , cancer research , biology , signal transduction , endoplasmic reticulum , extracellular matrix , physics , optics
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/β‐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.