Hu Kongzu, Sun Heyan, Gui Binjie, Sui Cong
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui 230032, PR China.
Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui 230032, PR China.
Biomed Pharmacother. 2017 Jul;91:841-848. doi: 10.1016/j.biopha.2017.04.094. Epub 2017 May 11.
Mechanical cues have been shown to induce osteogenic differentiation of bone marrow stromal cells (MSCs). The TRPV4 channel, a Ca-permeable membrane ion channel, is implicated in the transduction of external mechanical stimulation into specific intracellular responses in a wide variety of bone cells. However, the role of TRPV4 in transducing and regulating the differentiation of human MSCs in response to flow shear stress (FSS) is unclear. In this study, using FSS and calcium imaging, we demonstrated that FSS activated early osteogenic differentiation, as shown by the early osteogenic differentiation marker osterix (Osx) and alkaline phosphatase (ALP) staining. Increases in intracellular Ca and in the percentage of responding cells were induced by FSS. However, the late osteogenic differentiation marker Ocn and in vitro mineralization were unchanged after FSS stimulation. TRPV4 channels mediated the FSS-induced Ca influx and osteogenic differentiation of MSCs, which were inhibited by a selective TRPV4 blocker HC-067047 and specific Trpv4 siRNA. Ca influx through TRPV4 promoted NFATc1 nuclear localization. These results identify an essential role of TRPV4 in FSS-induced early osteogenic differentiation of human MSCs.
机械信号已被证明可诱导骨髓间充质干细胞（MSCs）的成骨分化。TRPV4通道是一种Ca²⁺通透的膜离子通道，参与将外部机械刺激转化为多种骨细胞中的特定细胞内反应。然而，TRPV4在转导和调节人MSCs响应流体剪切力（FSS）的分化中的作用尚不清楚。在本研究中，我们使用FSS和钙成像表明，FSS激活了早期成骨分化，早期成骨分化标志物osterix（Osx）和碱性磷酸酶（ALP）染色显示了这一点。FSS诱导细胞内Ca²⁺增加和响应细胞百分比增加。然而，FSS刺激后晚期成骨分化标志物Ocn和体外矿化没有变化。TRPV4通道介导了FSS诱导的MSCs的Ca²⁺内流和成骨分化，这被选择性TRPV4阻滞剂HC-067047和特异性Trpv4 siRNA所抑制。通过TRPV4的Ca²⁺内流促进了NFATc1的核定位。这些结果确定了TRPV4在FSS诱导的人MSCs早期成骨分化中的重要作用。
