Transcutaneous carbon dioxide improves joint inflammation and articular cartilage degeneration in rat osteoarthritis models

Abstract Background As global aging increases, and with life expectancy increases, both osteoarthritis (OA) prevalence and incidence is expected to rise. Transcutaneous carbon dioxide (CO 2 ) therapy has been shown to promote muscle regeneration, healing of fractures, strengthening of athletic endurance, recovery from peripheral nerve damage, and cancer. However, its effect on symptom modification and inflammation in OA is largely unknown. The objective of this study was to examine whether CO 2 therapy could slow progression of OA and relieve OA-related inflammation in a chemically or surgically induced model in rats. Question/purposes Using chemically and surgically induced models of OA, we sought to clarify whether transcutaneous carbon dioxide therapy improves OA-related inflammation and suppresses degeneration of articular cartilage. Methods OA model was induced by intra-articular injection of monosodium iodoacetate (MIA) and surgically induced by destabilization of the medial meniscus (DMM) in the knee joint. The pathogenesis period of MIA was set at 2 weeks, and that of DMM at 4 weeks. After the creation of the osteoarthritis model, either CO 2 therapy or sham intervention was applied daily for 20 minutes, and treatment was applied at 2 weeks. At the end of the intervention period, behavioral assessments were completed and then knee joints were harvested. Non-demineralized frozen sections were prepared and samples were examined histologically. Results Assessments of knee joint diameter showed that knee swelling in the DMM model improved significantly after 2 weeks of CO 2 therapy compared to the control group. The histomorphometric evaluation showed a significant increase in chondrocyte density in the CO 2 group compared to the MIA and DMM groups. Furthermore, the number of matrix metalloproteinases 13, a disintegrin and metalloproteinase with thrombospondin motifs 5, proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 positive cells decreased in the CO 2 group, while the number of aggrecan and type II collagen positive cells increased. Conclusions Our results clearly demonstrate that transcutaneous CO 2 therapy improves OA-related inflammation and suppresses degeneration of articular cartilage. Clinical Relevance Transcutaneous application of CO 2 may have therapeutic potential for improving articular inflammation and degeneration of articular cartilage in OA patients.