Intervertebral disc degeneration (IDD) is characterized by the decrease of nucleus pulposus cells (NPCs).With the increase of the degree of degeneration, the reactive oxygen species (ROS) in nucleus pulposus tissue increases. Pyroptosis is a newly discovered form of cell death and its relationship with oxidative stress in NPCs remains unclear. This study was performed to investigate the mechanisms of pyroptosis of NPCs under oxidative stress. NPCs were isolated from IDD patients by surgical treatment. Pyroptosis related proteins like NLR family pyrin domain containing 3(NLRP3) and PYD and CARD domain containing (PYCARD) were detected by western blot, and membrane pore formation was observed by hochest33342/PI double staining or scanning electron microscope. The results showed that ROS induced the pyroptosis of NPCs and it depended on the expression of NLRP3 and PYCARD. The increased ROS level also increased transcription factor nuclear factor, erythroid 2 like 2 (NFE2L2, Nrf2) and the autophagy of NPCs, both of which attenuated the pyroptosis. In summary, ROS induces the pyroptosis of NPCs through the NLRP3/ PYCARD pathway, and establishes negative regulation by increasing autophagy and NFE2L2. These findings may provide a better understanding of the mechanism of IDD and potential therapeutic approaches for IDD treatment.
The present study was performed to compare the clinical efficacy of lateral plate and lateral and medial double-plating fixation of distal femoral fractures and explore the indication of lateral and medial double-plating fixation of the distal femoral fractures. From March 2006 to April 2014, 48 and 12 cases of distal femoral fractures were treated with lateral plate (single plate) and lateral and medial plates (double plates), respectively. During the surgery, after setting the lateral plate for the distal femoral fractures, if the varus stress test of the knee was positive and the lateral collateral ligament rupture was excluded, lateral and medial double-plating fixation was used for the stability of the fragments. All the patients were followed up at an average period of 15.9 months. The average operation time, the intraoperative hemorrhage and the fracture union time of the two groups were compared. One year after operation, knee function was evaluated by the Kolmert’s standard. There was no significant difference in the average operation time, intraoperative hemorrhage, fracture healing time and excellent and good rates of postoperative knee function between two groups. Positive Varus stress test during operation can be an indication for lateral and medial double-plating fixation of distal femoral fractures.
Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase‐1 (HO‐1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO‐1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO‐1 expression was reduced in IDD tissues and replicative senescent NP cells. HO‐1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3‐MA pretreatment reversed the anti‐senescent and protective effects on the mitochondrial function of HO‐1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO‐1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO‐1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.