Correlation analysis of mircoRNA-210/hypoxia inducible factor-1α signaling axis and intervertebral disc degeneration

English Keywords:Lumbar disc herniation  Intervertebral disc degeneration  Hypoxia  Hypoxia inducible factor-1α  MircoRNA-210

English Abstract:

  【Abstract】 Objectives: To investigate the correlation between the microRNA-210(miR-210)/hypoxia inducible factor-1α(HIF-1α) signaling axis and intervertebral disc degeneration. Methods: From January to December 2024, 45 patients with lumbar disc herniation(LDH) who underwent surgical treatment for nucleus pulposus removal in the Department of Orthopedics and Traumatology, Suzhou Traditional Chinese Medicine Hospital were selected. There were 22 males and 23 females, aged 20 to 75 years[59(45, 67) years]. The disease duration was 1 to 240 months[36(9, 120) months]. Preoperative imaging data and the removed nucleus pulposus samples during operation were collected. The degeneration degree of the surgical intervertebral discs was graded using the Pfirrmann classification system on the sagittal MRI T2-weighted images; Hematoxylin-eosin(HE) staining was performed on the fixed sections of the nucleus pulposus to observe the pathological changes of the intervertebral discs and conduct histological scoring; Quantitative reverse transcription polymerase chain reaction(qRT-PCR) was used to detect the mRNA expression levels of miR-210-3p, HIF-1α, and glycerol-3-phosphate dehydrogenase 1-like(GPD1L) in the nucleus pulposus tissue; Immunohistochemical staining was used to detect the protein expression levels of HIF-1α and GPD1L in the nucleus pulposus tissue. The correlations between age, disease duration, histological scores and Pfirrmann grading, as well as the correlations between miR-210-3p, HIF-1α, GPD1L expression levels and intervertebral disc degeneration degree and miR-210-3p, HIF-1α, GPD1L were analyzed. Results: Pfirrmann grades of the surgical intervertebral discs of the 45 patients were: 4 cases of grade Ⅱ, 14 cases of grade Ⅲ, 19 cases of grade Ⅳ, and 8 cases of grade Ⅴ. Pfirrmann grading was positively correlated with age and disease duration(rs=0.763, P<0.001; rs=0.715, P<0.001). The pathological histological scores of nucleus pulposus were: 3.00±0.54 in Pfirrmann grade Ⅱ, 5.14±0.60 in grade Ⅲ, 8.58±0.74 in grade Ⅳ, and 9.54±0.75 in grade Ⅴ groups. The differences between groups were statistically significant(F=136.540, P<0.001), and the histological scores were positively correlated with Pfirrmann grade(rs=0.889, P<0.001). The expression levels of miR-210-3p, HIF-1α mRNA, HIF-1α protein, GPD1L mRNA, and GPD1L protein in nucleus pulposus tissue differed significantly among different Pfirrmann grades(P<0.05). The expression of miR-210-3p in nucleus pulposus tissue was positively correlated with Pfirrmann grade and histological score(rs=0.890, P<0.001; rs=0.832, P<0.001). The mRNA and protein expression of HIF-1α was positively correlated with Pfirrmann grade and histological score(rs=0.874, P<0.001; rs=0.821, P<0.001, and rs=0.868, P<0.001; rs=0.820, P<0.001). The mRNA and protein expression of GPD1L was negatively correlated with Pfirrmann grade and histological score(rs=-0.807, P<0.001; rs=-0.722, P<0.001, and rs= -0.793, P<0.001; rs=-0.718, P<0.001). The expression of miR-210-3p was positively correlated with HIF-1α mRNA expression(rs=0.839, P<0.001), and negatively correlated with GPD1L mRNA expression(rs=-0.776, P<0.001). HIF-1α expression was negatively correlated with both mRNA and protein expression of GPD1L(rs= -0.813, P<0.001, and rs=-0.754, P<0.001). Conclusions: The miR-210/HIF-1α signaling axis is associated with the degree of intervertebral disc degeneration, miR-210-3p, GPD1L and HIF-1α interact with each other and jointly participate in intervertebral disc degeneration.