Combined Effects of Nano-Pioglitazone and Bortezomib on Osteoarthritis Progression: An Experimental Study in a Rat...

Osteoarthritis (OA) is the most common degenerative joint disorder, affecting millions worldwide. It is characterized by progressive cartilage degradation and hypertrophic changes in the bone. Despite extensive research, no definitive cure exists, and understanding OA pathophysiology is crucial for developing novel therapies.

This study aimed to investigate the effects of Pioglitazone and Bortezomib, individually and in combination, on OA progression in a rat model.

Thirty-six male Sprague-Dawley rats underwent medial meniscectomy and anterior cruciate ligament transection to induce OA. Rats were randomly assigned to four groups: (1) intra-articular nano-Pioglitazone, (2) intra-articular Bortezomib, (3) combination of both drugs, and (4) control receiving normal saline. Histological assessment (Chambers score) and biochemical analyses of oxidative stress and inflammatory markers (MDA, IL-17, NF-κB) were performed.

No significant difference was observed in joint surface degeneration between the nano-Pioglitazone group and the control group (p = 0.09). Significant improvements were detected in the Bortezomib-treated group and combination therapy group compared to the control (p < 0.000001). Combination therapy showed significant improvement over nano-Pioglitazone alone (p < 0.000001) but was not significantly superior to Bortezomib monotherapy (p = 0.61). Biochemical analysis demonstrated that MDA, IL-17, and NF-κB levels were significantly reduced in the combination therapy group compared with control and single-drug groups (p < 0.0001).

These findings suggest that targeting oxidative stress and inflammatory signaling pathways, particularly NF-κB-mediated mechanisms, may play a critical role in mitigating OA progression. While combination therapy enhanced biochemical outcomes, its lack of additional structural benefit over bortezomib alone indicates that biochemical improvement does not necessarily translate into superior cartilage preservation within the studied timeframe.

Combined administration of nano-pioglitazone and bortezomib reduced inflammatory and oxidative stress markers and improved antioxidant activity in the OA model. Histological evaluation indicated reduced synovial inflammation and cartilage damage; however, no significant structural superiority was observed compared with bortezomib monotherapy. These findings suggest that the primary benefit of the combination therapy may lie in its biochemical effects, warranting further investigation in future studies.