骨髓间充质干细胞与 TGF-β 信号在骨重塑中的作用。
Bone marrow mesenchymal stem cells and TGF-β signaling in bone remodeling.
出版信息
J Clin Invest. 2014 Feb;124(2):466-72. doi: 10.1172/JCI70050. Epub 2014 Feb 3.
Abstract
During bone resorption, abundant factors previously buried in the bone matrix are released into the bone marrow microenvironment, which results in recruitment and differentiation of bone marrow mesenchymal stem cells (MSCs) for subsequent bone formation, temporally and spatially coupling bone remodeling. Parathyroid hormone (PTH) orchestrates the signaling of many pathways that direct MSC fate. The spatiotemporal release and activation of matrix TGF-β during osteoclast bone resorption recruits MSCs to bone-resorptive sites. Dysregulation of TGF-β alters MSC fate, uncoupling bone remodeling and causing skeletal disorders. Modulation of TGF-β or PTH signaling may reestablish coupled bone remodeling and be a potential therapy.
摘要
在骨吸收过程中，大量先前埋藏在骨基质中的因子被释放到骨髓微环境中，这导致骨髓间充质干细胞（MSCs）的募集和分化，以进行随后的骨形成，从而在时间和空间上偶联骨重塑。甲状旁腺激素（PTH）协调许多直接指导 MSC 命运的信号通路的信号。破骨细胞骨吸收过程中基质 TGF-β的时空释放和激活招募 MSCs 到骨吸收部位。TGF-β的失调改变了 MSC 的命运，使骨重塑解偶联，并导致骨骼疾病。TGF-β或 PTH 信号的调节可能重建偶联的骨重塑，并且是一种潜在的治疗方法。
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