Osteoarthritis (OA) is a prevalent joint disorder characterized by progressive cartilage degradation, impaired mesenchymal stem cell (MSC) function, and chronic inflammation, ultimately leading to irreversible structural damage and functional impairment. Despite its high global burden, no regulatory agency has yet approved a disease-modifying therapy for OA, and effective interventions to halt or delay its progression remain a major challenge. Recent research highlights the pivotal role of the immune system in OA pathogenesis, with immunomodulatory biomaterials emerging as a promising strategy to simultaneously regulate inflammatory responses and promote tissue regeneration. These biomaterials, by leveraging their biocompatibility and immunoregulatory properties, offer a transformative alternative to conventional OA therapies, which predominantly focus on symptom management rather than targeting the underlying disease mechanisms. In this review, we comprehensively examine various immunomodulatory biomaterial strategies designed to mitigate OA progression. We first elucidate the immune landscape of OA, detailing the interplay between inflammation and disease pathophysiology. Next, we explore the latest advancements in immunomodulatory biomaterials, including nanoparticles (NPs), hydrogels, and scaffolds, highlighting their potential to reshape OA treatment. Finally, we discuss existing challenges and propose future directions for optimizing biomaterial-based immunotherapies to enhance OA management.

Ageing significantly contributes to osteoarthritis (OA) and metabolic syndrome (MetS) pathogenesis, yet the underlying mechanisms remain unknown. This study aimed to identify ageing-related biomarkers in OA patients with MetS. OA and MetS datasets and ageing-related genes (ARGs) were retrieved from public databases. The limma package was used to identify differentially expressed genes (DEGs), and weighted gene coexpression network analysis (WGCNA) screened gene modules, and machine learning algorithms, such as random forest (RF), support vector machine (SVM), generalised linear model (GLM), and extreme gradient boosting (XGB), were employed. The nomogram and receiver operating characteristic (ROC) curve assess the diagnostic value, and CIBERSORT analysed immune cell infiltration. We identified 20 intersecting genes among DEGs of OA, key module genes of MetS, and ARGs. By comparing the accuracy of the four machine learning models for disease prediction, the SVM model, which includes CEBPB, PTEN, ARPC1B, PIK3R1, and CDC42, was selected. These hub ARGs not only demonstrated strong diagnostic values based on nomogram data but also exhibited a significant correlation with immune cell infiltration. Building on these findings, we have identified five hub ARGs that are associated with immune cell infiltration and have constructed a nomogram aimed at early diagnosing OA patients with MetS.

Chondrocytes are indispensable for the function of cartilage because they provide the extracellular matrix. Therefore, gaining insight into the chondrocytes may be helpful in understanding cartilage function and pinpointing potential therapeutical targets for diseases. The talus is a part of the ankle joint, which serves as the major large joint that bears body weight. Compared with the distal tibial and fibula, the talus bears much more mechanical loading, which is a risk factor for osteoarthritis (OA). However, in most individuals, OA seems to be absent in the ankle, and the cartilage of the talus seems to function normally. This study applied single-cell RNA sequencing to demonstrate atlas for chondrocyte subsets in healthy talus cartilage obtained from five volunteers, and chondrocyte subsets were annotated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for each cell type, cell–cell interactions, and single-cell regulatory network inference and clustering for each cell type were conducted, and hub genes for each cell type were identified. Immunohistochemical staining was used to confirm the presence and distribution of each cell type. Two new chondrocyte subsets were annotated as MirCs and SpCs. The identified and speculated novel microenvironment may pose different directions in chondrocyte composition, development, and metabolism in the talus.

Diabetic osteoporosis (DOP) represents a significant skeletal complication of diabetes mellitus characterized by compromised bone quality and increased fracture risk. Autophagy, a conserved cellular homeostatic mechanism, serves as a key regulator of bone formation and resorption balance. This review comprehensively examines the pivotal role of autophagy in DOP pathogenesis and explores emerging therapeutic strategies targeting autophagic regulation. Under hyperglycemic conditions, dysregulated autophagy occurs through multiple signaling pathways, including ROS-mTOR, PINK1/Parkin-mediated mitophagy, FoxO transcription factors, AGEs-RAGE and TLR4/NF-κB cascades etc. These disturbances manifest distinctly in various cell types: impaired mineralization of osteoblasts, altered bone resorption of osteoclasts, compromised insulin secretion of pancreatic β-cells, diminished osteogenic differentiation of bone marrow mesenchymal stem cells and adipose-derived stem cells. Current therapeutic approaches targeting autophagy dysregulation include pharmacological interventions such as metformin, rapamycin and vitamin D analogs, autophagy enhancers such as resveratrol and AMPK activators, specific inhibitors regulating excessive autophagic activity, Chinese medicinal compounds and exercise regimens. Emerging strategies also include gene therapy, stem cell transplantation and combined therapeutic approaches that precisely modulate the dynamic balance of autophagic flux. Moreover, we underscore the critical importance of maintaining optimal autophagic activity—neither excessive nor insufficient—in bone cells to preserve metabolic homeostasis and prevent osteoporotic progression in DOP patients. Future research directions should focus on elucidating specific mechanisms of action, identifying optimal intervention timing and exploring synergistic therapeutic combinations to effectively manage this challenging metabolic bone disorder.