What question did this study set out to answer?

This research aims to explore how diabetes mellitus exacerbates osteoarthritis by examining cellular and molecular changes.

June 2, 2026Bone and Joint Research0 citationsOpen Access

The transcriptional atlas, intercellular communication, and metabolic reprogramming of the cartilage and synovium in osteoarthritis patients with diabetes mellitus

YWYinxian Wen SLS Liu HCH Chen

Key Points

This research aims to explore how diabetes mellitus exacerbates osteoarthritis by examining cellular and molecular changes.
Conducted single-cell RNA sequencing, bulk RNA sequencing, and metabolome profiling on samples from 21 patients with OA or T2DMOA.
Analyzed transcriptional differences and intercellular signaling networks in knee cartilage and synovium.
Investigated pathways related to energy metabolism and fibroblast differentiation.
T2DMOA patients showed enhanced differentiation of sublining fibroblasts into lining fibroblasts, indicating altered cellular activity.
Notable intercellular communication pathways increased in T2DMOA, including HGF-MET and FGF10-FGFR1.
Cartilage in T2DMOA exhibited reduced metabolic activity, particularly in amino acid transport.

Abstract

Aims A strong correlation has been observed between diabetes mellitus (DM) with the pathogenesis of osteoarthritis (OA). This study aimed to elucidate the cellular and molecular mechanisms by which DM exacerbates OA, through multiomics analysis of synovium and cartilage from OA patients with type 2 DM (T2DMOA). Methods Single-cell RNA sequencing, bulk RNA sequencing, and metabolome profiling were performed on knee cartilage and synovium from 21 patients with OA or T2DMOA to investigate the differences in transcriptional landscape, intercellular signalling networks, transcription factor regulatory patterns, and alterations in metabolic pathways. Results Single-cell profiling of synovium-cartilage tissues revealed distinct pathological alterations in T2DMOA patients compared to non-diabetic OA controls. In the T2DMOA synovium, we observed significantly enhanced differentiation of sublining fibroblasts into lining fibroblasts, along with enriched pathways governing energy metabolism, vasculogenesis, and cell proliferation. For cell-cell communication between cartilage and synovium, hepatocyte growth factor ( HGF )-mesenchymal-epithelial transition factor ( MET ), fibroblast growth factors ( FGF ) 10-FGF receptor 1 ( FGFR1 ), and nicotinamide phosphoribosyl transferase ( NAMPT )-(integrin subunit alpha 5 ( ITGA5 ) + integrin subunit beta 1 ( ITGB1 )) from synoviocytes to chondrocytes, as well as angiopoietin-like protein 2 ( ANGPTL2 )-toll-like receptor 4 ( TLR4 ) and ANGPTL2- ( ITGA5 + IGTB1 ) from chondrocytes to synoviocytes, showed a notable increase in T2DMOA patients. Conversely, T2DMOA cartilage exhibited a pronounced suppression of metabolic activity, particularly in amino acid transport and glycan biosynthesis. Additionally, transcription factors of synoviocytes and chondrocytes were clustered into five and four major modules, respectively, with various functions. Conclusion Our findings define a diabetes-specific OA phenotype, characterized by aberrant synovial fibroblast activation, dysregulated synovium-cartilage crosstalk, and impaired cartilage metabolism. This integrated view establishes T2DMOA as a unique metabolic-subtype of OA, driven by disrupted intercellular communication and metabolic reprogramming. Cite this article: Bone Joint Res 2026;15(6):584–600.

问 AI

Bookmark

View Full Paper