Yexin Wang

Objectives: Temporomandibular osteoarthritis (TMJ OA) is a degenerative disease with pain, abnormal sound, and restricted mouth - opening. Oxidative stress and ferroptosis contribute to its progression, and inflammatory macrophages in the synovium are crucial. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4), a major Reactive Oxygen Species (ROS) source, is involved in joint disorders, but the mechanism of Nox4 regulating macrophage ferroptosis in TMJ OA is unclear. Method: RNA-sequencing was performed on synovial tissues obtained from patients or rats with or without TMJ OA to identify potential therapeutic targets for TMJ OA. Synovial tissues were examined histologically after staining with immunofluorescence. The impact of silencing Nox4 gene expression on inflammatory macrophages was explored. RT-qPCR and Western blotting were used to evaluate the expression of inflammatory and antioxidant genes. Intracellular and mitochondrial ROS were detected using DCFH-DA, DHE, or MitoSOX probes. Mitochondrial membrane potential was detected using the JC-1 probe. Lipid peroxidation and ferroptosis were measured using C11-BODIPY and FerroOrange. RNA-seq was used to analyze the anti-inflammatory mechanisms of the Nox4 inhibitor GLX351322 (40 μM) in LPS-stimulated macrophages. Results: In this study, we observed a marked upregulation of Nox4 expression in synovial macrophages from both TMJ OA patients and rats. Inhibition of Nox4 significantly attenuated inflammatory responses through activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Upon inhibition of Nox4, ROS production was reduced, accompanied by a reduction in mitochondrial damage. Meanwhile, Nox4 inhibition decreased ferroptosis in inflammatory macrophages by mitigating oxidative stress-induced lipid peroxidation. Conclusion: In this study, we identified Nox4 as a potential therapeutic target in TMJ OA. Targeting Nox4 counld reduce macrophage inflammation by alleviating oxidative stess-induced ferroptosis.

Inflammatory osteolysis is primarily characterized by an extensive macrophage-mediated inflammatory response coupled with osteoclast (OC) formation, triggered by bacterial byproducts and/or environmental stressors. And Osteoarthritis (OA) is one of the most common degenerative diseases in clinical medicine. Currently, anti-inflammatory drugs and intra-articular drug injection are mainly used, but the treatments only relieve symptoms. Punicalagin (PUN), a hydrolyzable tannin derived from pomegranate extract, the suppression of pro-inflammatory cytokine production in macrophages. The therapeutic potential of PUN in alleviating inflammatory osteolysis remains inadequately elucidated. PUN demonstrated favourable biocompatibility and therapeutic potential in vitro, including potent anti-osteoclastic activity, ROS scavenging capacity, and epigenetic regulatory functions. PUN was found to inhibit bromodomain-containing protein 4 (Brd4)-mediated chromatin space remodeling, consequently upregulating the production of endogenous anti-inflammatory factors and antioxidant factors. This study reveals a new therapeutic mechanism that PUN exerts anti-inflammatory effects and regulates epigenetic regulation by influencing Brd4-mediated chromatin remodeling. These findings showed the therapeutic potential of PUN for inflammatory diseases, especially inflammatory osteolysis. Notably, our work identifies a new strategy that synergistically combines osteoclast inhibition with epigenetic regulation, providing a promising direction for the therapies for bone-related inflammatory diseases.

Anchorage is one of the most important treatments for severe temporomandibular joint disorder (TMD). Anchoring nails have shown great success in clinical trials; however, they can break under pressure and are difficult to remove. In this study, we aimed to evaluate an improved anchoring nail and its mechanical stability. The experiment consisted of two parts: a tensile test and finite element analysis (FEA). First, traditional and improved anchoring nails were implanted into the condylar cortical bone and their tensile strength was measured using a tension meter. Second, a three-dimensional finite element model of the condyles with implants was established and FEA was performed with forces from three different directions. The FEA results showed that the total force of the traditional and improved anchoring nails is 48.2 N and 200 N, respectively. The mean (±s.d.) maximum tensile strength of the traditional anchoring nail with a 3–0 suture was 27.53 ± 5.47 N. For the improved anchoring nail with a 3–0 suture it was 25.89 ± 2.64 N and with a 2–0 suture it was above 50 N. The tensile strengths of the traditional and improved anchoring nails with a 3–0 suture was significantly different (P = 0.033–< 0.05). Furthermore, the difference between the traditional anchoring nail with a 3–0 suture and the improved anchoring nail with a 2–0 suture was also significantly different (P = 0.000–< 0.01). The improved anchoring nail, especially when combined with a 2–0 suture, showed better resistance ability compared with the traditional anchoring nail.