Tax1 binding protein 3 regulates osteogenic and adipogenic differentiation through inactivating Wnt/β-catenin signalling.
Tax1 binding protein 3 regulates osteogenic and adipogenic differentiation through inactivating Wnt/β-catenin signalling.
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DOI：
10.1111/jcmm.17702
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发表时间：
2023-04
影响因子：
5.3
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中科院分区：
文献类型：
--
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Tax1结合蛋白3 （Tax1bp3）是一种在癌症中过表达的含有PDZ结构域的蛋白。先前的研究认为Tax1bp3是β - catenin的抑制剂。目前尚不清楚Tax1bp3是否调控间充质祖细胞的成骨和脂肪分化。在目前的研究中，数据显示Tax1bp3在骨中表达，当诱导成骨细胞和脂肪细胞分化时，在祖细胞中表达增加。祖细胞中Tax1bp3的过表达抑制成骨分化，反过来刺激成脂分化，而Tax1bp3的低表达则反过来影响祖细胞的分化。体外实验使用来自成骨细胞特异性敲入小鼠的原代颅骨成骨细胞也证明了Tax1bp3的抗成骨和促脂肪功能。机制研究表明，Tax1bp3抑制典型Wnt/β‐catenin和骨形态发生蛋白(BMPs)/Smads信号通路的激活。综上所述，目前的研究提供的证据表明，Tax1bp3使Wnt/β‐catenin和bmp /Smads信号通路失活，并相互调节间充质祖细胞的成骨和脂肪分化。Wnt/β - catenin信号的失活可能参与了Tax1bp3的相互作用。
Tax1 binding protein 3 (Tax1bp3) is a PDZ domain‐containing protein that is overexpressed in cancer. Previous studies recognized Tax1bp3 as an inhibitor of β‐catenin. Till now it is not known whether Tax1bp3 regulates osteogenic and adipogenic differentiation of mesenchymal progenitor cells. In the current study, the data showed that Tax1bp3 was expressed in bone and was increased in the progenitor cells when induced toward osteoblast and adipocyte differentiation. The overexpression of Tax1bp3 in the progenitor cells inhibited osteogenic differentiation and conversely stimulated adipogenic differentiation, and the knockdown of Tax1bp3 affected the differentiation of the progenitor cells oppositely. Ex vivo experiments using the primary calvarial osteoblasts from osteoblast‐specific Tax1bp3 knock‐in mice also demonstrated the anti‐osteogenic and pro‐adipogenic function of Tax1bp3. Mechanistic investigations revealed that Tax1bp3 inhibited the activation of canonical Wnt/β‐catenin and bone morphogenetic proteins (BMPs)/Smads signalling pathways. Taken together, the current study has provided evidences demonstrating that Tax1bp3 inactivates Wnt/β‐catenin and BMPs/Smads signalling pathways and reciprocally regulates osteogenic and adipogenic differentiation from mesenchymal progenitor cells. The inactivation of Wnt/β‐catenin signalling may be involved in the reciprocal role of Tax1bp3.
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