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Loss of Axin1 in limb mesenchymal cells leads to multiple synostoses syndrome-like phenotype in mice

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    1. Loss-of-Axin1 or Axin1/Axin2 in limb MSCs in mice results in a phenotype resembling SYNS.

      Loss-of-Axins in limb MSCs in mice lead to the activation of β-catenin-BMP signaling in the cKO mice model.

      The SYNS phenotype in Axin1 cKO mice could be partially reversed by β-catenin or BMP signaling inhibitor.

      The genetic mouse model with SYNS-like phenotype could serve as important tools for SYNS disease.

  • Multiple synostoses syndrome (SYNS) is a disease characterized by the fusion of multiple joints. Unfortunately, the underlying and critical signaling pathways of this disorder remain poorly understood. Given the pivotal role of Wnt/β-catenin signaling in skeletal development and the key regulatory effect of Axin1 and Axin2 in the β-catenin pathway, limb mesenchymal stem cell (MSC) specific Axin1 conditional KO (cKO) mice and Axin1/Axin2 double KO (dKO) mice were generated to explore their involvement in joint formation. Abnormalities, such as developmental defects in joints and fusions in multiple joint tissues were observed in both Axin1 cKO and Axin1/Axin2 dKO mice, which resemble to the characteristics of human SYNS disease including synostoses of carpal and tarsal bones, as well as ankylosis of elbow joint and knee joint. Administration of β-catenin or BMP inhibitor significantly reversed the joint fusion phenotype in Axin1 cKO mice. Our findings suggest that Axin1 plays a key role in joint formation by inhibiting β-catenin-BMP signaling and could potentially serve as a therapeutic target for SYNS.
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  • Cite this article:

    Yi D., Xie R., Zeng D., et al., (2024). Loss of Axin1 in limb mesenchymal cells leads to multiple synostoses syndrome-like phenotype in mice. The Innovation Medicine 2(1): 100053. https://doi.org/10.59717/j.xinn-med.2024.100053
    Yi D., Xie R., Zeng D., et al., (2024). Loss of Axin1 in limb mesenchymal cells leads to multiple synostoses syndrome-like phenotype in mice. The Innovation Medicine 2(1): 100053. https://doi.org/10.59717/j.xinn-med.2024.100053

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