A Lox/CHOP-10 crosstalk governs osteogenic and adipogenic cell fate by MSCs.
A Lox/CHOP-10 crosstalk governs osteogenic and adipogenic cell fate by MSCs.
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Lox/CHOP-10 串扰通过 MSC 控制成骨和脂肪形成细胞的命运
DOI：
10.1111/jcmm.13798
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发表时间：
2018-10
影响因子：
5.3
通讯作者：
Huang HY
中科院分区：
文献类型：
--
作者：
Jiang WY;Xing C;Wang HW;Wang W;Chen SZ;Ning LF;Xu X;Tang QQ;Huang HY
加速的骨髓脂肪生成与衰老和骨质疏松症有关，被认为是由于间充质干细胞（MSCs）成脂和成骨分化之间的不平衡。我们之前已经发现赖氨酰氧化酶（Lox）抑制破坏BMP 4诱导的脂肪细胞谱系定型和MSC分化。在这项研究中，我们发现lox抑制显著上调BMP 4诱导的CCAAT/增强子结合蛋白（C/EBP）同源蛋白10（CHOP-10）的表达，然后促进BMP 4诱导的体外和体内MSC成骨。具体而言，Lox抑制或CHOP-10上调激活Wnt/β-catenin信号传导以增强BMP 4诱导的成骨，而促脂肪形成p38 MAPK和Smad信号传导受到抑制。总之，我们证明了Lox/CHOP-10串扰调节BMP 4诱导的MSC成骨和成脂命运决定，为骨质疏松症和其他骨骼疾病提供了有希望的治疗靶点。
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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