The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation.
The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation.
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IHH下调对软骨细胞生长和分化的抑制作用。
DOI：
10.3892/etm.2017.5458
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发表时间：
2018-01
影响因子：
2.7
通讯作者：
Guo C
中科院分区：
文献类型：
--
作者：
Deng A;Zhang H;Hu M;Liu S;Wang Y;Gao Q;Guo C
软骨细胞的增殖率影响骨的延长。软骨细胞肥大是软骨内骨形成所必需的，因为软骨细胞分泌成骨细胞分化和成熟所需的因子。先前的研究表明，印度刺猬（Ihh）信号通路是骨骼发育和稳态的关键调节因子。本研究旨在探讨Ihh在软骨细胞增殖和分化中的作用及其机制。使用短发夹RNA在小鼠软骨细胞中敲除Ihh。流式细胞仪检测软骨细胞凋亡和细胞周期阻滞，结果表明，与阴性对照组相比，Ihh基因敲低可显著抑制软骨细胞的生长（P<0.05），增加软骨细胞的凋亡（P<0.001）。Ihh的下调也导致软骨细胞的细胞周期停滞在G1至S期。敲低Ihh可降低软骨细胞的碱性磷酸酶活性和矿物质沉积。Ihh下调对软骨细胞生长和分化的抑制作用可能与转化生长因子-β/母体抗十肢瘫痪和骨保护素/核因子κB受体激活剂配体信号通路有关。本研究的结果表明，软骨细胞衍生的Ihh是必不可少的维持骨生长板和Ihh表达或其信号成分的操纵可能是一种新的治疗技术，用于治疗骨骼疾病，包括软骨发育不全。
The proliferative rate of chondrocytes affects bone elongation. Chondrocyte hypertrophy is required for endochondral bone formation as chondrocytes secrete factors required for osteoblast differentiation and maturation. Previous studies have demonstrated that the Indian hedgehog (Ihh) signaling pathway is a key regulator of skeletal development and homeostasis. The aim of the present study was to investigate the function of Ihh in chondrocyte proliferation and differentiation, as well as the underlying mechanisms. Ihh was knocked down in mouse chondrocyte cells using short hairpin RNA. Chondrocyte apoptosis and cell cycle arrest were assessed using flow cytometry and the results indicated that knockdown of Ihh significantly inhibited cell growth (P<0.05) and increased apoptosis (P<0.001) compared with negative control cells. Downregulation of Ihh also resulted in cell cycle arrest at G1 to S phase in chondrocytes. It was also observed that knockdown of Ihh decreased alkaline phosphatase activity and mineral deposition of chondrocytes. The inhibitory roles of Ihh downregulation on chondrocyte growth and differentiation may be associated with the transforming growth factor-β/mothers against decapentaplegic and osteoprotegerin/receptor activator of nuclear factor κB ligand signaling pathway. The results of the present study suggest that chondrocyte-derived Ihh is essential for maintaining bone growth plates and that manipulation of Ihh expression or its signaling components may be a novel therapeutic technique for the treatment of skeletal diseases, including achondroplasia.
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