TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation.
TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation.
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骨重塑依赖于骨吸收和随后骨形成的精确协调。这一过程的紊乱与骨骼疾病有关，如Camurati-Engelmann病（CED）。我们通过体外和动物模型表明，骨吸收过程中释放的活性TGF-β1通过诱导骨髓基质细胞（也称为骨间充质干细胞（BMSCs））向骨吸收部位迁移来协调骨形成，这一过程是通过SMAD信号通路介导的。对携带ced衍生的TGF-β1突变的小鼠模型（表现出典型的进行性骨干发育不良伴胫骨骨折）进行分析，我们发现骨髓中活性TGF-β1水平较高。用TGF-β I型受体抑制剂治疗可部分恢复非偶联骨重塑并防止骨折。因此，由于TGF-β1具有骨吸收和骨形成的偶联作用，调节TGF-β1活性可能是骨重塑疾病的有效治疗方法。
Bone remodeling depends on the precise coordination of bone resorption and subsequent bone formation. Disturbances of this process are associated with skeletal diseases, such as Camurati-Engelmann disease (CED). We show using in vitro and animal models that active TGF-β1 released during bone resorption coordinates bone formation by inducing migration of bone marrow stromal cells, also known as bone mesenchymal stem cells (BMSCs) to the bone resorptive sites and that this process is mediated through SMAD signaling pathway. Analysis of a mouse model carrying a CED-derived TGF-β1 mutation, which exhibits the typical progressive diaphyseal dysplasia with tibial fractures, we found high levels of active TGF-β1 in the bone marrow. Treatment with a TGF-β type I receptor inhibitor partially rescued the uncoupled bone remodeling and prevented the fractures. Thus, as TGF-β1 functions to couple bone resorption and formation, modulation of TGF-β1 activity could be an effective treatment for the bone remodeling diseases.
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影响因子：
3.6
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