Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China.
J Cell Biochem. 2018 Nov;119(11):9316-9326. doi: 10.1002/jcb.27208. Epub 2018 Aug 3.
Osteoarthritis is the most frequent chronic bone and joint diseases in older populations all over the world. Lipopolysaccharide (LPS)-induced murine chondrogenic ATDC5 cell model has been widely used for testing new osteoarthritis therapeutic targets. This study aimed to explore the effects of microRNA-136 (miR-136) on LPS-induced ATDC5 cell injury and inflammatory cytokine expression, as well as underlying potential mechanism. We found that LPS remarkably inhibited ATDC5 cell viability, induced ATDC5 cell apoptosis, and upregulated the expression of inflammatory cytokines, including interleukin 1β (IL-1β), IL-6, IL-8, and tumor necrosis factor α (TNF-α; P < .01 or < .001). Moreover, LPS obviously upregulated the expression of miR-136 in ATDC5 cells (P < .05). Overexpression of miR-136 markedly exacerbated the LPS-induced ATDC5 cell viability inhibition, cell apoptosis enhancement, and inflammatory cytokine expression (P < .05), and suppression of miR-136 had opposite effects (P < .05). Myeloid cell leukemia 1 (Mcl-1) was a direct target gene of miR-136, which participated in the effect of miR-136 on LPS-induced ATDC5 cell inflammatory injury. Overexpression of Mcl-1 alleviated the LPS-induced inactivation of Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways, while suppression of Mcl-1 had opposite effects. To conclude, this study verified that miR-136 promoted LPS-induced ATDC5 cell injury and inflammatory cytokine expression by targeting Mcl-1, and Mcl-1 was involved in the regulatory effects of LPS on Wnt/β-catenin and JAK/STAT signaling pathways in ATDC5 cells.
骨关节炎是全世界老年人群中最常见的慢性骨骼和关节疾病。脂多糖 (LPS)-诱导的鼠 ATDC5 软骨细胞模型已广泛用于测试新的骨关节炎治疗靶点。本研究旨在探讨 microRNA-136 (miR-136) 对 LPS 诱导的 ATDC5 细胞损伤和炎症细胞因子表达的影响，以及潜在的潜在机制。我们发现 LPS 显著抑制 ATDC5 细胞活力，诱导 ATDC5 细胞凋亡，并上调炎症细胞因子的表达，包括白细胞介素 1β (IL-1β)、IL-6、IL-8 和肿瘤坏死因子 α (TNF-α；P < .01 或 < .001)。此外，LPS 明显上调 ATDC5 细胞中 miR-136 的表达 (P < .05)。miR-136 的过表达显著加剧了 LPS 诱导的 ATDC5 细胞活力抑制、细胞凋亡增强和炎症细胞因子表达 (P < .05)，而 miR-136 的抑制则产生相反的效果 (P < .05)。髓样细胞白血病 1 (Mcl-1) 是 miR-136 的直接靶基因，参与了 miR-136 对 LPS 诱导的 ATDC5 细胞炎症损伤的作用。Mcl-1 的过表达减轻了 LPS 诱导的 Wnt/β-catenin 和 Janus 激酶/信号转导和转录激活因子 (JAK/STAT) 信号通路的失活，而 Mcl-1 的抑制则有相反的效果。总之，本研究验证了 miR-136 通过靶向 Mcl-1 促进 LPS 诱导的 ATDC5 细胞损伤和炎症细胞因子表达，而 Mcl-1 参与了 LPS 对 ATDC5 细胞 Wnt/β-catenin 和 JAK/STAT 信号通路的调节作用。
