Knockdown of Indian hedgehog protein induces an inhibition of cell growth and differentiation in osteoblast MC3T3‑E1 cells.
Knockdown of Indian hedgehog protein induces an inhibition of cell growth and differentiation in osteoblast MC3T3‑E1 cells.
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敲低印度刺猬蛋白会诱导成骨细胞MC3T3 − E1细胞的细胞生长和分化的抑制作用。
DOI：
10.3892/mmr.2017.7669
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发表时间：
2017-12
影响因子：
3.4
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;Gao Q;Wang Y;Guo C
印度刺猬蛋白（Ihh）是进化上保守的，在控制祖细胞向成骨细胞分化中起重要作用。Ihh无效突变小鼠表现出软骨内骨成骨细胞发育失败。虽然研究表明Ihh信号是一个有效的局部因子，调节成骨细胞分化，但决定成骨细胞分化的特异性转录因子仍不清楚。需要进一步的研究来确定Ihh调节成骨细胞分化的确切机制。本研究采用短发夹RNA（shorthairpin RNA，shRNA）技术敲低成骨细胞MC 3 T3-E1中的Ihh，探讨Ihh在成骨细胞增殖和分化中的作用，并探讨Ihh诱导成骨细胞凋亡和细胞周期阻滞的可能机制。与阴性对照组相比，Ihh的敲低诱导了细胞生长的显著抑制，并增加了细胞凋亡率。Ihh的下调导致成骨细胞的细胞周期停滞在G1至S期边界。此外，Ihh的敲低降低了成骨细胞的碱性磷酸酶活性和矿物质沉积。Ihh下调对成骨细胞生长和分化的抑制作用可能与转化生长因子-β/母体对十肢瘫同源物和肿瘤坏死因子受体超家族成员11B/肿瘤坏死因子配体超家族成员11信号通路有关。操纵Ihh表达或其信号组分可能对骨骼疾病的治疗有益。
Indian hedgehog protein (Ihh) is evolutionarily conserved and serves important roles in controlling the differentiation of progenitor cells into osteoblasts. Ihh null mutant mice exhibit a failure of osteoblast development in endochondral bone. Although studies have demonstrated that Ihh signaling is a potent local factor that regulates osteoblast differentiation, the specific transcription factors that determine osteoblast differentiation remain unclear. Further studies are required to determine the precise mechanism through which Ihh regulates osteoblast differentiation. In the present study, Ihh was knocked down in osteoblast MC3T3-E1 cells using short hairpin RNA, to investigate the function of Ihh in osteoblast proliferation and differentiation and to examine the potential mechanism through which Ihh induces osteoblast apoptosis and cell cycle arrest. It was observed that the knockdown of Ihh induced a marked inhibition of cell growth and increased the apoptosis rate compared with the negative control osteoblasts. Downregulation of Ihh resulted in a cell cycle arrest at the G1 to S phase boundary in osteoblasts. In addition, the knockdown of Ihh decreased the alkaline phosphatase activity and mineral deposition of osteoblasts. The inhibitory roles of Ihh downregulation in osteoblast growth and differentiation may be associated with the transforming growth factor-β/mothers against decapentaplegic homolog and tumor necrosis factor receptor superfamily member 11B/tumor necrosis factor ligand superfamily member 11 signaling pathways. Manipulating either Ihh expression or its signaling components may be of benefit for the treatment of skeletal diseases.
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