ABSTRACT
Backgroud: Iron overload is a prevalent condition in the elderly, often associated with various degenerative diseases, including intervertebral disc degeneration (IDD). Nevertheless, the mechanisms responsible for iron ion accumulation in tissues and the mechanism that regulate iron homeostasis remain unclear. Transferrin receptor-1 (TFR1) serves as the primary cellular iron gate, playing a pivotal role in controlling intracellular iron levels, however its involvement in IDD pathogenesis and the underlying mechanism remains obscure. Methods: Firstly, IDD mice model was established to determine the iron metabolism associated proteins changes during IDD progression. Then CEP chondrocytes were isolated and treated with TBHP or pro-inflammatory cytokines to mimic pathological environment, western blotting, immunofluorescence assay and tissue staining were employed to explore the underlying mechanisms. Lastly, TfR1 siRNA and Feristatin II were employed and the degeneration of IDD was examined using micro-CT and immunohistochemical analysis. Results: We found that the IDD pathological environment, characterized by oxidative stress and pro-inflammatory cytokines, could enhance iron influx by upregulating TFR1 expression in a HIF-2α dependent manner. Excessive iron accumulation not only induces chondrocytes ferroptosis and exacerbates oxidative stress, but also triggers the innate immune response mediated by c-GAS/STING, by promoting mitochondrial damage and the release of mtDNA. The inhibition of STING through siRNA or the reduction of mtDNA replication using ethidium bromide alleviated the degeneration of CEP chondrocytes induced by iron overload. Conclusion: Our study systemically explored the role of TFR1 mediated iron homeostasis in IDD and its underlying mechanisms, implying that targeting TFR1 to maintain balanced iron homeostasis could offer a promising therapeutic approach for IDD management. The translational potential of this article: Our study demonstrated the close link between iron metabolism dysfunction and IDD, indicated that targeting TfR1 may be a novel therapeutic strategy for IDD.
ABSTRACT
OBJECTIVE: To define the characteristics of Mini LDH, develop new diagnostic references and examine the clinical efficacy of percutaneous endoscopic lumbar discectomy via a transforaminal approach (TF-PELD) for it. METHODS: A total of 72 patients who underwent TF-PELD with Mini LDH from September 2019 to October 2022 were enrolled in this retrospective study. The patients' basic information, symptoms, number of outpatient visits, duration of conservative treatment, physical examination findings and so on were obtained from the medical records. Clinical effects of TF-PELD for Mini LDH were assessed by means of the following: the Visual Analog Scale (VAS) for low back pain (LBP) and leg pain, Oswestry Disability Index (ODI) for functional status assessment and Modified Mac Nab criteria for patient satisfaction. RESULTS: Mini LDH have specific clinical characteristics and imaging features. All included patients achieved obvious pain relief after TF-PELD surgery. Pain scores were repeated at postoperative day 1 and 1, 3, 6, 12 and 24 months later. Results were statistically analyzed. The average VAS-Back, VAS-Leg and ODI scores were all significantly reduced at the first postoperative day and gradually decreased with the follow-up time continuing. In total, 66 out of 72 patients received an excellent or good recovery and no poor result was reported according to the Modified Mac Nab criteria. CONCLUSIONS: Mini LDH is a type of LDH with special characteristics and in need of correct diagnosis and active treatment in clinical work. TF-PELD was also found to be an effective procedure for the treatment of Mini LDH.
