Stage-dependent analysis of IL-6, TGF-β, osteocalcin, and sRANKL in the synovial fluid of dogs with osteoarthritis

Abstract

Abstract Osteoarthritis (OA) is traditionally considered a degenerative joint disease. However, morphological similarities between OA progression and fracture healing suggest that OA may be a dysregulated bone repair process. This study investigated the morphological and biochemical parallels between OA and bone healing in dogs following cranial cruciate ligament rupture. To differentiate between biochemical profiles at different stages of the disease, a structured OA scoring system was developed based on radiographic and additional intraoperative findings. Synovial fluid samples from the OA cohort were analysed for IL-6, TGF-β, osteocalcin and sRANKL. IL-6 concentrations decreased significantly with advancing OA severity ( p  = 0.0068), suggesting a shift from inflammatory to reparative mechanisms. TGF-β, osteocalcin and sRANKL demonstrated stage-dependent trends consistent with osteogenic and remodelling activity. However, these associations did not reach statistical significance. The combined morphological and biomarker findings suggest that OA progression exhibits features similar to the phases of bone healing, which are characterised by dynamic interactions between inflammation, resorption, and bone formation. Nevertheless, the predominantly non-significant biomarker correlations highlight the need for larger sample sizes and longitudinal studies to confirm these observations and further clarify causal mechanisms. These results support the concept that OA may represent a chronic but dysregulated adaptive repair response to joint damage, rather than a purely degenerative process.