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Peer-reviewedCC BY-NC-NDBMC musculoskeletal disorders

Integrated serum and synovial biomarker profiling reveals inflammatory and cartilage remodeling signatures in age-restricted knee osteoarthritis.

7 affiliations
  1. 1Department of Orthopaedics and Traumatology, Fırat University, Elazığ, Türkiye. [email protected].
  2. 2Department of Orthopaedics and Traumatology, Fırat University, Elazığ, Türkiye.
  3. 3Department of Medical Biochemistry, Kafkas University, Kars, Türkiye.
  4. 4Elazığ Training and Research Hospital, Elazığ, Türkiye.
  5. 5Fırat University, Elazığ, Türkiye.
  6. 6Department of Biostatistics and Medical Informatics, Faculty of Medicine, Fırat University, Elazığ, Türkiye.
  7. 7Department of Anesthesiology and Reanimation, Elazığ Training and Research Hospital, Elazığ, Türkiye.

Abstract

Purpose

Knee osteoarthritis (OA) is a complex disease characterized by inflammation, cartilage degeneration, and tissue remodeling. Although many biomarkers have been investigated, the combined biological significance of systemic and local biomarkers is not fully understood. This study aimed to comprehensively address serum and synovial biomarkers associated with inflammation, cartilage turnover, and metabolic regulation in patients with knee OA.Methods

Seventy-five participants (40 knee OA patients and 35 surgical controls) were prospectively included in the study. Serum and synovial fluid levels of IL-6, TNF-α, COMP, PIINP, Spexin, Asprosin, and Klotho were measured using ELISA. Intergroup comparisons were performed using the Mann-Whitney U test, correlations were evaluated using Spearman correlation analysis, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis.Results

Serum IL-6 demonstrated excellent diagnostic performance, showing the highest discriminative ability (AUC = 0.962). Serum Spexin (AUC = 0.782) and COMP (AUC = 0.661) showed moderate discriminative performance. In synovial fluid, COMP (AUC = 0.733), IL-6 (AUC = 0.701), and PIINP (AUC = 0.687) showed significant but moderate diagnostic accuracy. Correlation analyses indicated that there may be significant associations between adipokines and inflammatory and cartilage-related biomarkers.Conclusion

Integrated evaluation of serum and synovial biomarkers supports the concept that osteoarthritis involves inflammatory and tissue remodeling pathways. IL-6 showed the strongest discriminative performance overall, while COMP and PIINP reflected the stage-dependent cartilage remodeling process. These findings improve the biological characterization of advanced knee osteoarthritis and may contribute to future biomarker-based patient classification methods.

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BibTeX
@article{key2026integrated,
  title = {{Integrated serum and synovial biomarker profiling reveals inflammatory and cartilage remodeling signatures in age-restricted knee osteoarthritis.}},
  author = {Sefa Key and Erhan Yılmaz and Huseyin Fatih Gul and Anıl Agar and Omer Esmez and Osman Sedat Tanyeri and Mehmet Onur Kaya and Nurgul Cetgen Key},
  journal = {BMC musculoskeletal disorders},
  year = {2026},
  month = aug,
  doi = {10.1186/s12891-026-10310-4},
  url = {https://europepmc.org/article/MED/42958523},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Integrated serum and synovial biomarker profiling reveals inflammatory and cartilage remodeling signatures in age-restricted knee osteoarthritis.
AU  - Sefa Key
AU  - Erhan Yılmaz
AU  - Huseyin Fatih Gul
AU  - Anıl Agar
AU  - Omer Esmez
AU  - Osman Sedat Tanyeri
AU  - Mehmet Onur Kaya
AU  - Nurgul Cetgen Key
PY  - 2026
DA  - 2026/08/01
JO  - BMC musculoskeletal disorders
DO  - 10.1186/s12891-026-10310-4
UR  - https://europepmc.org/article/MED/42958523
AB  - Purpose  Knee osteoarthritis (OA) is a complex disease characterized by inflammation, cartilage degeneration, and tissue remodeling. Although many biomarkers have been investigated, the combined biological significance of systemic and local biomarkers is not fully understood. This study aimed to comprehensively address serum and synovial biomarkers associated with inflammation, cartilage turnover, and metabolic regulation in patients with knee OA.Methods  Seventy-five participants (40 knee OA patients and 35 surgical controls) were prospectively included in the study. Serum and synovial fluid levels of IL-6, TNF-α, COMP, PIINP, Spexin, Asprosin, and Klotho were measured using ELISA. Intergroup comparisons were performed using the Mann-Whitney U test, correlations were evaluated using Spearman correlation analysis, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis.Results  Serum IL-6 demonstrated excellent diagnostic performance, showing the highest discriminative ability (AUC = 0.962). Serum Spexin (AUC = 0.782) and COMP (AUC = 0.661) showed moderate discriminative performance. In synovial fluid, COMP (AUC = 0.733), IL-6 (AUC = 0.701), and PIINP (AUC = 0.687) showed significant but moderate diagnostic accuracy. Correlation analyses indicated that there may be significant associations between adipokines and inflammatory and cartilage-related biomarkers.Conclusion  Integrated evaluation of serum and synovial biomarkers supports the concept that osteoarthritis involves inflammatory and tissue remodeling pathways. IL-6 showed the strongest discriminative performance overall, while COMP and PIINP reflected the stage-dependent cartilage remodeling process. These findings improve the biological characterization of advanced knee osteoarthritis and may contribute to future biomarker-based patient classification methods.
SN  - 1471-2474
ER  -