A Lox/CHOP‐10 crosstalk governs osteogenic and adipogenic cell fate by MSCs |
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| Authors: | Wen‐yan Jiang Chun Xing Hong‐wei Wang Wei Wang Su‐zhen Chen Liu‐fang Ning Xu Xu Qi‐qun Tang Hai‐yan Huang |
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| Institution: | 1. Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Shanghai, China;2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China;3. Biliary and Pancreatic Center, Huadong Hospital, Fudan University, Shanghai, China;4. Institute of Stem Cell Research and Regenerative Medicine, Institutes of Biomedical Sciences, Fudan University, Shanghai, China |
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| 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/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. |
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| Keywords: | BAPN BMP4 CHOP‐10 Lox obesity osteoporosis |
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