Intervertebral disc degeneration (IVDD) is the leading cause of low back pain, where degeneration and death of nucleus pulposus cells within the intervertebral disc (IVD) can be obviously revealed. This degeneration can result in an imbalance in the extracellular matrix due to the loss of proteoglycans and water content, which can further lead to catabolic and anabolic dysfunction of the IVD. Recently, the dysfunction of cartilage endplate (CEP) during aging has drawn large attention due to its essential functions in contributing nutrient exchange and maintaining IVD homeostasis. Furthermore, the inflammation and disturbed homeostasis of CEP not only accelerate the degradation of nucleus pulposus extracellular matrix, but also exacerbate IVDD by causing nucleus pulposus cell death through other pathological factors. Here in this review, we summarized the possible pathological factors and the underlying mechanisms of the CEP inflammation-induced IVDD, including exosomes degeneration, CEP calcification, ferroptosis, mechanical changes, and cell senescence. Besides, changes of miRNAs, pain-related neural reflex arc and pathways associated with CEP inflammation-induced IVDD are also reviewed. In addition, new strategies specifically designed for CEP inflammation-induced IVDD are also discussed in the last section. We hope this paper can not only offer some new insights for advancing novel strategies for treating IVDD, but also serve as a valuable reference for researchers in this field.

Osteoarthritis (OA) is the most widespread joint disorder worldwide. It is a major cause of lower limb mobility issues in the elderly. With the ongoing aging of the global population and the increasing prevalence of obesity, the disease burden associated with OA is expected to rise significantly. E3 ubiquitin ligases (E3s) play a crucial role in protein ubiquitination. They identify specific substrates and attach ubiquitin molecules to substrates, thus modulating protein stability, function, and cellular localization. E3s can be classified into three main types: RING-, HECT-, and RBR-type E3s. Growing evidence indicates that E3s affect OA by regulating the degradation of extracellular matrix (ECM) proteins and inflammatory responses. This review highlights the functions and underlying mechanisms of E3s in OA, aiming to provide new therapeutic insights for the treatment of OA.

Objective: This study presented a comprehensive characterization of the osteomyelitis immune microenvironment, identified driver genes and pathogenic cell populations underlying disease progression, and uncovered potential therapeutic targets through single-cell and bulk transcriptomic analysis. Methods: We analyzed time-series transcriptomic sequencing data from mouse osteomyelitis samples in the dataset GSE168896. Fuzzy c-means clustering was applied to reveal gene sets linked to disease progression. Immune cell infiltration analysis was conducted through the online tool ImmuCellAI-mouse. Furthermore, by leveraging single-cell sequencing data, we characterized immune cell subpopulations and pinpointed the key cell subtypes that were present in the osteomyelitis mice. Results: We identified six gene clusters exhibiting distinct temporal expression patterns and functional roles in osteomyelitis, such as leukocyte and lymphocyte activation and ossification. Single-cell sequencing analysis further showed seven distinct cellular subpopulations. Among these, macrophages demonstrated a significant increase following osteomyelitis, and the infiltration of Mif ⁺ Cd63 ⁺ , Arg1 ⁺ Sdc4 ⁺ , and Cxcl1 ⁺ Ccl4 ⁺ macrophages significantly increased. Moreover, Ccl3–Ccr1 and Cxcl2–Cxcr2 ligand–receptors contributed mostly in immune cells. Conclusion: Our findings tracked the transcriptional dynamics and evolving immune landscape of osteomyelitis, highlighting macrophages as central regulators of disease progression. We identified that significant infiltration of Arg1 ⁺ Sdc4 ⁺ , Cxcl1 ⁺ Ccl4 ⁺ , and Mif ⁺ Cd63 ⁺ macrophages may affect osteomyelitis through the Ccl3–Ccr1 and Cxcl2–Cxcr2 signaling pathways. These findings offer a new perspective on immune regulation in osteomyelitis.

The formation and repair of bone tissue depend not only on the activity of bone tissue cells but also on complex regulatory mechanisms mediated by the immune system. With the advancements of osteoimmunology in recent years, the functional roles of metal ions in this field have attracted extensive attention. Various metal ions, including zinc, magnesium, manganese, strontium, and copper, are demonstrated to influence the osteoimmune microenvironment and promote bone repair by modulating the biological functions of immune cells, especially the inflammatory response. However, the precise mechanisms through which metal ions orchestrate osteoimmunity have not been fully elucidated, and the underlying signaling pathways, as well as their internal interactions with cells involved in bone repair, require further in-depth investigation. This review summarizes the regulatory effects of various metal ions on macrophages, T cells, dendritic cells, and neutrophils, including phenotype polarization, maturation, differentiation, inflammatory cytokine expression, and underlying signaling pathways. Besides, this review further discusses the application of metal ion-doped biomaterials in bone tissue engineering, while also covers their functions in remodeling the osteoimmune microenvironment and highlights potential directions for future research directions.