Zhou Xianwei, Li Jitian, Teng Junyan, Liu Yufeng, Zhang Di, Liu Linyun, Zhang Wenming
Spine Surgery, Luoyang Orthopedic Hospital of Henan Province, No. 100 Yongping Road, Henan, 450000, Zhengzhou, China.
Laboratory of Bone Tumor, Luoyang Orthopedic Hospital of Henan Province, Henan, 450000, Zhengzhou, China.
Inflamm Res. 2021 Mar;70(3):297-308. doi: 10.1007/s00011-021-01434-5. Epub 2021 Jan 23.
Intervertebral disc degeneration (IDD) is a key element resulting in low back pain, but the mechanisms underlying IDD remain largely unknown. The purpose of the study was to investigate the influence of microRNA-155-3p (miR-155-3p) on proliferation and autophagy of nucleus pulposus (NP) cells in IDD with the involvement of hypoxia-inducible factor 1 α (HIF1α)/histone lysine demethylase 3A (KDM3A) axis.
IDD NP tissues of patients with lumbar disc herniation and traumatic intervertebral disc NP tissues from patients with traumatic lumbar fracture were collected. Apoptosis in NP tissues was observed, and autophagy marker proteins in NP tissues were detected. NP cells in IDD were transfected with miR-155-3p mimic or KDM3A-siRNA to explore their roles in cell proliferation, autophagy and apoptosis. MiR-155-3p, KDM3A and HIF1α expression in NP tissues and cells were detected.
Decreased miR-155-3p, and elevated HIF1α and KDM3A were presented in NP tissues and cells of IDD. Elevated miR-155-3p or silenced KDM3A promoted the proliferation and autophagy, and inhibited the apoptosis of NP cells of IDD. Moreover, elevated miR-155-3p decreased KDM3A and HIF1α expression, while silenced KDM3A decreased HIF1α expression in NP cells with IDD.
The study concludes that up-regulated miR-155-3p or silenced KDM3A promotes the proliferation, autophagy, and restrains the apoptosis of NP cells of IDD via inhibition of HIF1α, which may be a promising approach for the treatment of IDD.
椎间盘退变（IDD）是导致腰痛的关键因素，但其潜在机制仍不清楚。本研究旨在探讨微小RNA-155-3p（miR-155-3p）在缺氧诱导因子1α（HIF1α）/组蛋白赖氨酸去甲基化酶3A（KDM3A）轴参与下对IDD中髓核（NP）细胞增殖和自噬的影响。
收集腰椎间盘突出症患者的IDD NP组织和创伤性腰椎骨折患者的创伤性椎间盘NP组织。观察NP组织中的细胞凋亡，并检测NP组织中的自噬标记蛋白。用miR-155-3p模拟物或KDM3A-siRNA转染IDD中的NP细胞，以探讨它们在细胞增殖、自噬和凋亡中的作用。检测NP组织和细胞中miR-155-3p、KDM3A和HIF1α的表达。
IDD的NP组织和细胞中miR-155-3p表达降低，HIF1α和KDM3A表达升高。miR-155-3p升高或KDM3A沉默促进了IDD中NP细胞的增殖和自噬，并抑制了其凋亡。此外，miR-155-3p升高降低了KDM3A和HIF1α的表达，而KDM3A沉默降低了IDD中NP细胞的HIF1α表达。
本研究得出结论，上调miR-155-3p或沉默KDM3A可通过抑制HIF1α促进IDD中NP细胞的增殖、自噬，并抑制其凋亡，这可能是一种有前景的IDD治疗方法。
