骨细胞
细胞凋亡
细胞生物学
兰克尔
生物
破骨细胞
成骨细胞
半胱氨酸蛋白酶3
基因敲除
癌症研究
程序性细胞死亡
体外
受体
生物化学
激活剂(遗传学)
作者
Xiwen Song,Yi Tang,Jie Zhu,Yuanye Tian,Zhao-Hui Song,Xiu Feng Hu,Chaoyue Hong,Yun Cai,Feiwu Kang
出处
期刊:Tissue & Cell
[Elsevier]
日期:2020-12-01
卷期号:67: 101402-101402
被引量:22
标识
DOI:10.1016/j.tice.2020.101402
摘要
Apoptotic osteocytes were found in the hypoxic bone microenvironment in osteoporosis, osteotomy, orthodontic tooth movement and periodontitis, and played a key role in bone remolding and the differentiation of osteoclasts. Hypoxia inducible factor-1α(HIF-1α), as a transcription factor under hypoxic conditions, has been confirmed to participate in cell apoptosis. However, the effect of HIF-1α on osteocytes apoptosis and the osteocyte-mediated osteoclast formation remains elusive. Here, we hypothesized that HIF-1α was involved in osteocytes apoptosis. Our results showed that CoCl2 increased the MLO-Y4 cells apoptosis by upregulating the proapoptotic gene expression of caspase-3. Moreover, siRNA-mediated knockdown of HIF-1α decreased the phosphorylation by JNK and the activation of caspase-3 to inhibit the cell apoptosis in MLO-Y4. Furthermore, SP600125, an inhibitor of JNK, reversed CoCl2-induced the increased apoptosis of MLO-Y4 cells in term of reducing the expression of caspase-3. These findings revealed that HIF-1α served as a pro-apoptotic factor in the apoptosis of MLO-Y4 cells cultured with CoCl2, by activating the JNK/caspase-3 signaling pathway. Besides, the osteocyte-mediated osteoclastogenesis was reduced with the decline of the expression of HIF-1α and caspase-3 in MLO-Y4 cells. Our study provided an idea for a more comprehensive understanding of HIF-1α and the process of bone remodeling.
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