SOD2 orchestrates redox homeostasis in intervertebral discs: A novel insight into oxidative stress-mediated degeneration and therapeutic potential.

Low back pain (LBP) is a pervasive global health concern, primarily associated with intervertebral disc (IVD) degeneration. Although oxidative stress has been shown to contribute to IVD degeneration, the underlying mechanisms remain undetermined. This study aimed to unravel the role of superoxide dismutase 2 (SOD2) in IVD pathogenesis and target oxidative stress to limit IVD degeneration. SOD2 demonstrated a dynamic regulation in surgically excised human IVD tissues, with initial upregulation in moderate degeneration and downregulation in severely degenerated IVDs. Through a comprehensive set of in vitro and in vivo experiments, we found a suggestive association between excessive mitochondrial superoxide, cellular senescence, and matrix degradation in human and mouse IVD cells. We confirmed that aging and mechanical stress, established triggers for IVD degeneration, escalated mitochondrial superoxide levels in mouse models. Critically, chondrocyte-specific Sod2 deficiency accelerated age-related and mechanical stress-induced disc degeneration in mice, and could be attenuated by ß-nicotinamide mononucleotide treatment. These revelations underscore the central role of SOD2 in IVD redox balance and unveil potential therapeutic avenues, making SOD2 and mitochondrial superoxide promising targets for effective LBP interventions.

Investigation of the Mitigation of DMSO-Induced Cytotoxicity by Hyaluronic Acid following Cryopreservation of Human Nucleus Pulposus Cells.

To develop an off-the-shelf therapeutic product for intervertebral disc (IVD) repair using nucleus pulposus cells (NPCs), it is beneficial to mitigate dimethyl sulfoxide (DMSO)-induced cytotoxicity caused by intracellular reactive oxygen species (ROS). Hyaluronic acid (HA) has been shown to protect chondrocytes against ROS. Therefore, we examined the potential of HA on mitigating DMSO-induced cytotoxicity for the enhancement of NPC therapy. Human NPC cryopreserved in DMSO solutions were thawed, mixed with equal amounts of EDTA-PBS (Group E) or HA (Group H), and incubated for 3-5 h. After incubation, DMSO was removed, and the cells were cultured for 5 days. Thereafter, we examined cell viability, cell proliferation rates, Tie2 positivity (a marker of NP progenitor cells), and the estimated numbers of Tie2 positive cells. Fluorescence intensity of DHE and MitoSOX staining, as indicators for oxidative stress, were evaluated by flow cytometry. Group H showed higher rates of cell proliferation and Tie2 expressing cells with a trend toward suppression of oxidative stress compared to Group E. Thus, HA treatment appears to suppress ROS induced by DMSO. These results highlight the ability of HA to maintain NPC functionalities, suggesting that mixing HA at the time of transplantation may be useful in the development of off-the-shelf NPC products.

Minimally Invasive 360° Fusion Using a Combination of INFIX and Minimally Invasive Spinopelvic Fixation by Intraoperative Computed Tomography Navigation for Unstable Pelvic Ring Fracture: A Technical Note.

OBJECTIVE: Fluoroscopy is often used in the surgery of unstable pelvic ring fractures, and improved safety in implant placement is an issue. An anterior subcutaneous pelvic fixator (INFIX) combined with a percutaneous screw has been reported to be a minimally invasive and effective surgical technique for unstable pelvic ring injuries. However, although percutaneous screw fixation is minimally invasive, its indications for fracture fixation and fractures with large fragment displacements in the vertical plane remain controversial. Therefore, this technical note aims to describe a new technique for unstable pelvic ring fractures. METHODS: We describe a 360° fusion of the pelvic ring to treat unstable pelvic ring fractures, including vertical shear pelvic ring fractures, using an intraoperative CT navigation system. Seven patients were treated with 360° fusion for type C pelvic ring fractures. In surgery, after reducing the fracture with external fixation, intraoperative CT navigation is used to perform a 360° fusion with INFIX and minimally invasive surgical spinopelvic fixation (MIS-SPF). We will introduce a typical case and explain the procedure. RESULTS: A 360° fixation was performed, and no perioperative complications were noted. The mean blood loss was 253.2 ± 141.0 mL, and the mean operative time was 224.3 ± 67.4 min. In a typical case, bone union was obtained 1 year after surgery, and we removed all implants. CONCLUSIONS: MIS-SPF has a strong fixation force and helps reduce fractures' horizontal and vertical planes. In addition, 360° fusion with intraoperative CT navigation may help treat unstable pelvic ring fractures.