One of the causes of intervertebral disc degeneration (IVDD) is nucleus pulposus cell (NPC) death, possibly apoptosis. In this study, we explored the role of the Nrf2/Sirt3 pathway and tert‐butylhydroquinone (t‐BHQ) in IVDD and elucidated the potential working mechanism. Reactive oxygen species (ROS) assay kits and malondialdehyde (MDA) assay kits were used to assess oxidative stress. Western blot and TUNEL staining were used to examine apoptosis. After siRNA against Nrf2 or lentivirus against Sirt3 was transfected into NPCs, the mechanism of the effect of the Nrf2/Sirt3 pathway on NPCs was assessed. The interaction between t‐BHQ and its potential interacting protein NRF2 was further investigated through protein docking analysis. ChIP examined the binding affinity between Nrf2 and Sirt3 promoter. In vivo experiments, X‐ray, hematoxylin‐eosin (HE) staining, Safranin O staining, and immunohistochemistry were used to evaluate IVDD grades. The results demonstrated that activation of the Nrf2/Sirt3 pathway inhibited tert‐butyl hydroperoxide‐ (TBHP‐) induced apoptosis and mitochondrial dysfunction in vitro. In addition to apoptosis, upregulation of the Nrf2/Sirt3 pathway induced by t‐BHQ restored TBHP‐induced autophagic flux disturbances. However, its protective effect was reversed by chloroquine and Si‐ATG5. Furthermore, t‐BHQ ameliorated IVDD development in a rat model. In conclusion, our findings indicate that the Nrf2/Sirt3 pathway and its agonist represent a potential candidate for treating IVDD.

Immunometabolism, the regulation of immune cell function through metabolic pathways, has emerged as a key focus in regenerative medicine. Traditional bone healing therapies primarily target the osteoblast-osteoclast regulatory axis, overlooking the metabolic reprogramming of immune cells (e.g., macrophages) and limiting regenerative efficiency. Macrophages orchestrate bone healing through dynamic shifts between proinflammatory (M1-like) and reparative (M2-like) metabolic phenotypes. Recent studies have shown that their immunometabolic transitions govern the sequential phases of bone healing. Therefore, targeting macrophage immunometabolism may offer a novel therapeutic paradigm for bone regeneration. This review summarizes recent advances in understanding how macrophage metabolism regulates bone healing, emphasizing the critical role of immunometabolism in resolving inflammation and regenerating tissue throughout the repair process. By integrating insights from the fields of cellular metabolism, microenvironmental signals, and biomaterial science, this review aims to offer an integrative perspective on how targeting macrophage metabolic control could serve as a therapeutic strategy to enhance bone regeneration. This review addresses five core concepts. First, it delineates the spatiotemporal roles and phenotypic shifts of macrophages in the different phases of bone healing. Second, it explores how the reprogrammed metabolism of glucose, lipids, and amino acids underlies macrophage polarization and function. Third, it emphasizes how microenvironmental cues, including cytokines, metabolic intermediates, and microbiota-derived metabolites, modulate macrophage immunometabolism. Fourth, it summarizes emerging therapeutic strategies designed to regulate macrophage metabolism for bone regeneration, such as cell-based therapies, immunomodulatory hydrogels, and nanotechnologies. Finally, it identifies major challenges in this field. These include the temporal-spatial complexity of immunometabolism, the lack of human-relevant models, the emerging concepts of cross-system regulation, and the technological limitations in targeted regulation. Together, these insights provide a conceptual basis for future precision immunometabolic interventions in bone repair.

Aims: To explore the effect and mechanism of gastrodin (GAS) on human umbilical vein endothelial cells (HUVECs) apoptosis induced by oxidative stress and its function in wound healing. Main methods: HUVECs were incubated with tert-butyl hydroperoxide (TBHP) to induce endothelial cell dysfunction and GAS was used as a protector. Cell viability was detected by Counting Kit-8 (CCK-8). HUVECs apoptosis was evaluated by TUNEL assay and western blotting for cleaved caspase3 (C-caspase3) and other apoptosis-related proteins. Transwell migration assay, tube formation assay, and cell-matrix adhesion assay were performed to evaluated cell function of HUVECs. Transfection with nuclear factor-erythroid 2-related factor 2 (Nrf2) small interfering ribonucleic acid and western blotting for Nrf2, HO-1, and apoptosis-related proteins were performed to prove that Nrf2/HO-1 pathway is involved in the protective effects of GAS. The skin wound model of rat was used to assess the protective effects of GAS in vivo. Key Findings: The results show that treating HUVECs with GAS attenuated TBHP-induced apoptosis and cellular dysfunction, including cellular tube formation, migration, and adhesion. Mechanistically, we found that GAS protects HUVECs from TBHP-induced cellular apoptosis by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. An in vivo study illustrated that the oral administration of GAS enhances vascularization in regenerated tissue and facilitates wound healing. Significance: The findings of this study demonstrated that GAS may serve as a potential agent that accelerates wound healing.

Recently, as our population increasingly ages with more pressure on bone and cartilage diseases, bone/cartilage tissue engineering (TE) have emerged as a potential alternative therapeutic technique accompanied by the rapid development of materials science and engineering. The key part to fulfill the goal of reconstructing impaired or damaged tissues lies in the rational design and synthesis of therapeutic agents in TE. Gold nanomaterials, especially gold nanoparticles (AuNPs), have shown the fascinating feasibility to treat a wide variety of diseases due to their excellent characteristics such as easy synthesis, controllable size, specific surface plasmon resonance and superior biocompatibility. Therefore, the comprehensive applications of gold nanomaterials in bone and cartilage TE have attracted enormous attention. This review will focus on the biomedical applications and molecular mechanism of gold nanomaterials in bone and cartilage TE. In addition, the types and cellular uptake process of gold nanomaterials are highlighted. Finally, the current challenges and future directions are indicated.