gms | German Medical Science

Objectives: Osteoarthritis (OA) represents one of the most common pathologies in orthopedic surgery. However, pharmacologic treatment options are still lacking. Recent clinical studies described increased levels of the chemokine Cxcl9 in the synovial fluid of osteoarthritic knees. This study was thus conducted to investigate the pathophysiological role of Cxcl9 in experimental OA using a pre-clinical rodent model.

Methods: A standardized anterior cruciate ligament transection (ACLT) was carried out to induce post-traumatic OA in female WT and Cxcl9-deficient mice. After 4 and 8 weeks, respectively, the operated and the contralateral knees were collected and processed for radiological, histological, or gene expression analysis. Micro-computed tomography was used to evaluate changes in subchondral bone and osteophyte formation. Histological evaluation was performed to quantify cartilage degeneration and synovitis using semi-quantitative scores according to OARSI recommendations, in addition to the measurement of cellular osteoclast and osteoblast parameters in subchondral bone. Assessment of the expression of inflammatory markers as well as bone remodelling parameters of the whole knee was conducted via qRT-PCR.

Results and conclusion: Radiological assessment of the OA knees revealed no differences in subchondral bone structure between WT and Cxcl9-deficient mice. In contrast, osteophyte formation was significantly decreased in mice lacking Cxcl9 at all timepoints. Histologically, no differences in articular cartilage degeneration and synovial inflammation were observed between Cxcl9-deficient mice and WT mice 4 weeks postoperatively. At the 8-week timepoint after ACLT however, scoring of cartilage deterioration revealed a markedly reduced OA progression in mice lacking Cxcl9. In line with these findings, OA knees of Cxcl9-deficient mice displayed reduced synovial inflammation histologically and preserved cartilage markers on a transcriptional level.

In sum, our results show an attenuation of joint degeneration upon genetic inactivation of Cxcl9, demonstrating a disease-modifying role of Cxcl9 in experimental OA. Pharmacologic inhibition of Cxcl9 could therefore potentially represent a novel treatment option for OA.