Osteoarthritis (OA) is a chronic degenerative disease featured by cartilage erosion and inflammation. Luteolin, a member of the flavonoid family, has been shown to exert anti‐inflammatory and antioxidative activities. However, the potential biological effects and underlying mechanism of luteolin on chondrocytes and OA progression remain largely elusive. In this study, the potential effect and mechanism of luteolin on OA were investigated in vitro and in vivo. Our data revealed that luteolin inhibited H₂O₂‐induced cell death, apoptosis, oxidative stress, programmed necrosis, and inflammatory mediator production in primary murine chondrocytes. In addition, luteolin could activate the AMPK and Nrf2 pathways, and AMPK serves as a positive upstream regulator of Nrf2. In vivo results demonstrated the therapeutic effects of luteolin on OA in the DMM mouse model. Collectively, our findings showed that luteolin might serve as a novel and effective treatment for OA and provided a new research direction for clinical OA therapies.

Osteoarthritis (OA), widely seen in the elderly, is featured by cartilage degradation, subchondral bone remolding, and synovium inflammation. Currently, there is no cure for OA development. Phillygenin (PHI), an active ingredient from the Forsythiae Fructus, possesses many biological properties, such as anti-inflammation and anti-oxidative stress in several diseases. However, the potential effects and underlying mechanisms of PHI on OA remain unclear. Western blotting, RT-PCR, ELISA and tissue staining were employed to explore the mechanisms by which PHI exerted a protective effect on IL-1β-induced production of pro-inflammation cytokines and extracellular matrix (ECM) degradation in primary murine chondrocytes and destabilization of the medial meniscus (DMM) mouse models. In this study, we found that PHI inhibited the production of pro-inflammation cytokines and ECM degradation induced by IL-1β in primary murine chondrocytes. Mechanically, PHI inhibited the NF-κB pathway via activating nuclear factor (erythrluteolind-derived 2)-like 2 (Nrf2). In vivo experiments also confirmed the chondroprotection of PHI in DMM mouse models. PHI alleviated IL-1β-induced inflammation cytokines and ECM degradation via activating Nrf2 and inhibiting NF-κB pathway. This study provides a biological rationale for the use of PHI as a potential candidate for OA treatment.

Introduction: Chronic osteomyelitis remains a clinical challenge in orthopedics.Methods: In this study, silk fibroin microspheres (SFMPs) loaded with vancomycin are entrapped in an injectable silk hydrogel to form a vancomycin delivery system for treatment of chronic osteomyelitis.Results and Discussion: Vancomycin showed continuous release from the hydrogel for up to 25 days. The hydrogel shows strong antibacterial activity against both Escherichia coli and Staphylococcus aureus and a long antibacterial duration of 10 days without a decrease in the antibacterial effect. The injection of vancomycin-loaded silk fibroin microspheres entrapped in the hydrogel into the infected site of rat tibia reduced bone infection and improved bone regeneration compared with other treatment groups.Conclusion: Thus, the composite SF hydrogel features a sustained-release profile and good biocompatibility, making it promising for application in osteomyelitis treatment.

Nrf2 is a critical regulator of the antioxidant defense systems in cellular protection. Emerging evidence has shown that four‐octyl itaconate (OI) activates Nrf2 cascade. In this study, the chondroprotective effects of OI on H₂O₂‐stimulated chondrocytes and DMM‐induced osteoarthritis (OA) progression were investigated. In primary murine chondrocytes, OI interrupted the binding of Keap1 and Nrf2, leading to accumulation and nuclear translocation of Nrf2 protein, as well as transcription and expression of Nrf2‐dependent genes, such as HO-1, NQO1, and GCLC. Furthermore, OI inhibited cell death and apoptosis, as well as H₂O₂‐stimulated ROS generation, lipid peroxidation, superoxide accumulation, and mitochondrial depolarization in chondrocytes, which were abolished by the silence or depletion of Nrf2. In addition, in vivo experiments revealed the therapeutic effects of OI on OA progression in a DMM mouse model. Collectively, these results suggested that OI might serve as a potential treatment for OA progression.

Background: Radiation-induced myelopathy (RM) is a significant complication of radiotherapy with its mechanisms still not fully understood and lacking effective treatments. Compound 7 (C7) is a newly identified, potent, and selective inhibitor of the Keap1-Nrf2 interaction. This study aimed to explore the protective effects and mechanisms of C7 on RM in vitro and in vivo. Methods: Western blotting, quantitative real‐time polymerase chain reaction (qRT‐PCR), reactive oxygen species (ROS) and mitochondrial polarization, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, genetic editing techniques, locomotor functions, and tissue staining were employed to explore the protective effects and underlying mechanisms of C7 in radiation-induced primary rat microglia and BV2 cells, as well as RM rat models. Results: In this study, we found that C7 inhibited the production of pro-inflammation cytokines and oxidative stress induced by irradiation in vitro. Further, the data revealed that radiation worsened the locomotor functions in rats, and C7 significantly improved histological and functional recovery in RM rats. Mechanically, C7 activated Nrf2 signaling and promoted the microglia transformation from M1 to M2 phenotype. Conclusion: C7 could ameliorate RM by boosting Nrf2 signaling and promoting M2 phenotype microglia polarization in vitro and in vivo.