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.

在骨质疏松症、截骨术、正畸牙齿移动和牙周炎的缺氧骨微环境中发现凋亡的骨细胞，在骨重塑和破骨细胞分化中起关键作用。缺氧诱导因子-1α（HIF-1α）作为缺氧条件下的转录因子，已被证实参与细胞凋亡。然而，HIF-1α对骨细胞凋亡和骨细胞介导的破骨细胞形成的影响仍然难以捉摸。在这里，我们假设 HIF-1α 参与骨细胞凋亡。我们的结果表明 CoCl ₂通过上调caspase-3的促凋亡基因表达来增加MLO-Y4细胞的凋亡。此外，siRNA 介导的 HIF-1α 敲低降低了 JNK 的磷酸化和 caspase-3 的激活，以抑制 MLO-Y4 中的细胞凋亡。此外，JNK 抑制剂 SP600125通过降低 caspase-3 的表达来逆转 CoCl ₂诱导的 MLO-Y4 细胞凋亡增加。这些发现表明 HIF-1α 在用 CoCl ₂培养的 MLO-Y4 细胞凋亡中起促凋亡因子的作用，通过激活 JNK/caspase-3 信号通路。此外，随着MLO-Y4细胞中HIF-1α和caspase-3表达的下降，骨细胞介导的破骨细胞生成减少。我们的研究为更全面地了解 HIF-1α 和骨重塑过程提供了思路。