Regional Genetic Responses of Porcine Talar Articular Cartilage to Impact Injury

Abstract

Category:Ankle ArthritisIntroduction/Purpose:The ankle is at greatest risk for post-traumatic osteoarthritis (PTOA) in comparison to the hip or knee. Adaptive changes to the cartilaginous topography may be a marker for where cartilage damage poses the greatest risk of development of osteoarthritis. The objective of this study was to elucidate the mechanism of PTOA by analyzing the changes in regional genetic expression of inflammatory markers after impact injury in an ex-vivo porcine model.Methods:Talus bones were recovered from 5 porcine ankles. A drop tower was used to induce injury by dropping a 1000 g weight from a height of 15 cm on the talus. Following the injury the bone was cultured for 24 hours. Four 6-mm cartilage plugs were harvested from the inferior aspect of each talus bone and a small slice of each plug was used for cell imaging. The remaining cartilage plugs were flash frozen with liquid nitrogen and stored at -80°C for ribonucleic acid (RNA) extraction and analysis of gene expression. Expression of inflammatory and catabolic genes (IL1-ß, TNF-a, ADAMTS-5, ADAMTS-4, MMP-3 and MMP-13) was compared among the samples obtained from the non-impacted and impacted sites of the anterior and posterior regions. Student t-test was performed to examine the differences between the control (non-impact) and impacted samples from each region and between the control samples from the anterior and posterior regions.Results:The current porcine impact model demonstrated significant up-regulation of several inflammatory cytokines and metalloproteinases by impact force. Among the genes tested, TNF-a, ADAMTS-4, and MMP-3 showed increased expression at impact sites (p<0.05) compared to non-impact sites in the posterior region (Figure 1) whereas no differences were found in the anterior region. Interestingly, the non-impacted samples in the anterior region exhibited significantly higher expression of TNF-a, ADAMTS-4, MMP-3 and ADAMTS-5 than those of the posterior region (p<0.05).Conclusion:The results of the current ex-vivo porcine impact study demonstrate significant up-regulation of inflammatory and catabolic genes 24 hours after porcine talus bone impaction. These findings highlight the relevance of regional differences in post- traumatic ankle inflammation; the posterior region of porcine talar articular cartilage demonstrated increased sensitivity in response to injury. The anterior region illustrated greater resistance to injury, showing less gene up-regulation compared to the posterior region of the same ankle. These findings suggest that location of cartilage injury may play a crucial role in the development of inflammatory response, chondrocyte apoptosis, and subsequent osteoarthritis of the ankle.