Serum TSP-1 is a useful biomarker in severity assessment and the diagnosis of osteoarthritis

J Transl Med. 2025 Sep 2;23(1):987. doi: 10.1186/s12967-025-07022-z.

ABSTRACT

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. Thrombospondin-1 (TSP-1) is a secreted trimeric glycoprotein with multiple functions. It can bind to various cell-surface receptors and is downregulated in OA chondrocytes. However, the utility of TSP-1 as a biomarker for OA remains unclear. Therefore, we aimed to investigate the association between serum TSP-1 concentration and knee OA.

DESIGN: We quantified serum TSP-1 concentrations in mice with post-traumatic OA (PTOA) and age-dependent OA (ADOA) using enzyme-linked immunosorbent assay (ELISA). We statistically analyzed the correlation between TSP-1 concentration and OA severity. Additionally, we generated cartilage-specific TSP-1 knockout mice and assessed TSP-1 concentration in the serum. Finally, we measured the concentrations of TSP-1 in the serum and synovial fluid of patients with OA and conducted statistical analyses to evaluate the correlation between TSP-1 concentration and Outerbridge grading. ROC curve analysis was used to determine the diagnostic value of TSP-1 for OA.

RESULTS: Serum TSP-1 concentration was reduced in wild-type mice with PTOA or ADOA and negatively correlated with OA severity. In cartilage-specific TSP-1 knockout mice, serum TSP-1 levels were decreased. In patients with OA, serum and synovial fluid TSP-1 levels were reduced and negatively correlated with OA severity. These findings suggest that TSP-1 may serve as a potential biomarker for the diagnosis of OA.

CONCLUSION: Serum TSP-1 concentration is associated with OA severity in both mice and humans and may serve as a useful diagnostic biomarker for OA.

PMID:40898256 | DOI:10.1186/s12967-025-07022-z