Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha, Hunan 410078, P.R. China.
Mol Med Rep. 2017 Dec;16(6):7987-7992. doi: 10.3892/mmr.2017.7669. Epub 2017 Sep 29.
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.
印度刺猬蛋白（Ihh）在进化上是保守的，在控制祖细胞分化为成骨细胞方面发挥着重要作用。Ihh 缺失突变小鼠表现出软骨内骨中成骨细胞发育的失败。尽管研究表明 Ihh 信号是调节成骨细胞分化的有力局部因子，但决定成骨细胞分化的特定转录因子仍不清楚。需要进一步研究以确定 Ihh 调节成骨细胞分化的确切机制。在本研究中，使用短发夹 RNA 敲低成骨细胞 MC3T3-E1 中的 Ihh，以研究 Ihh 在成骨细胞增殖和分化中的功能，并研究 Ihh 诱导成骨细胞凋亡和细胞周期停滞的潜在机制。结果观察到，与阴性对照成骨细胞相比，Ihh 的敲低诱导细胞生长明显抑制，并增加了细胞凋亡率。Ihh 的下调导致成骨细胞在 G1 到 S 期边界的细胞周期停滞。此外，Ihh 的下调降低了成骨细胞的碱性磷酸酶活性和矿化沉积。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/抗颅足畸形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 的表达或其信号成分可能有益于骨骼疾病的治疗。
