## 4 Discussion  
Cytokine activity is a well-defined research area in OA, offering many potential therapeutic targets to be explored. Interleukin-15 (IL-15), a pro-inflammatory cytokine, with important roles in innate immunity, has increased levels in OA tissue and can potentially increase catabolic activity within the joint. Our study utilized a Holtzmann Sprague-Dawley male global _II15-/-_ model to study the contribution of IL-15 in PTOA progression. Our work demonstrated that _II15-/-_ rats present with normal joint morphology in the absence of surgery and display similar structural features of PTOA to their _II15+/+_ counterparts. Through the analysis of cartilage damage, subchondral bone damage, osteophyte formation, and synovitis we did not see any significant differences between genotypes, suggesting that IL-15 does not play a vital role in PTOA progression in this rat model, at least at the stage investigated. These data do not support our initial hypothesis. Weight was recorded as a measure of general health, especially for the PTOA group following surgery. There was no significant difference in weight at any timepoint between all groups, similar to the findings from [PERSON] et al. (2017) who compared weight of _II15+/-_ and _III15-/-_ female rats ([PERSON] et al., 2017). Even though the _II15+/_ PTOA rats lost weight during the first 4 days post-op, this loss was not statistically significant, and they continued to gain weight in the weeks following. Interestingly, the _II15-/-_ rats, in both the PTOA and Naive groups, consistently weighed less than their _II15+/+_ counterparts, although not enough to reach statistical significance. _II15-/-_ mice have varied in their reported weight differences in the literature; for example, [PERSON] et al. (2000) reported that _II15-/-_ mice were not significantly different in body weight compared to _II15+/+_ mice, but another study reported that female _II15-/-_ mice weighed less ([PERSON] et al., 2017; [PERSON] et al., 2017). Similarly, studies using _II15 Ra-/-_ mice have conflicting reports of weight, either reporting similar weights or a decrease in weight in mutants compared to controls ([PERSON] et al., 2017; [PERSON] et al., 2017). Interestingly, _II15-/-_ mice on a high fat diet are resistant to diet-induced weight gain due to increased thermogenic capacity in brown and beige fat cells ([PERSON] et al., 2017). Our male _II15-/-_ rats trend towards weighing less, perhaps due to a similar increased thermogenic capacity, although not enough to reach statistical significance at the timepoints used in our study. In order to assess PTOA progression, ACLT-DMM surgery was utilized in both _II15-/-_ and _III15+/+_ rats. Early stage PTOA was successfully induced 8 weeks following surgery, as determined by statistically higher scores for cartilage damage, subchondral bone damage, and osteophyte presence compared to the Naive group. As expected, the damage was generally contained to the more weight bearing medial compartment. There is also evidence of synovitis developing in the PTOA group, as they scored significantly higher for sub-synovial infiltration and surface fibrin deposition, compared to the Naive group. Overall, ACLT-DMM surgery successfully induced early PTOA. Inconsistent with our hypothesis, there was no significant difference between the _II15-/-_ and _II15+/+_ PTOA rats, indicating that IL-15 may not play a vital role in rat PTOA pathophysiology. This finding is also inconsistent with previous studies that found a relationship between IL-15 activity and OA, which may be due to a few factors. Firstly, it is possible that the rodent model is not ideal for translating studies in IL-15, as current literature on IL-15 and OA has exclusively been reported from human studies ([PERSON] et al., 2017; [PERSON] et al., 2017; [PERSON] et al., 2017; [PERSON] et al., 2017). Additionally, our study examined only the 8-week timepoint, but the activity of IL-15 may be more robust at an earlier or end stage of disease. Another pitfall could be due to differing OA phenotypes.