Background/Significance/Rationale: Over 6 million individuals are affected by post-traumatic osteoarthritis (PTOA) at an annual burden of $15 billion to the US healthcare system. Despite this, there are no disease-modifying therapies for the prevention or cure of PTOA. Cartilage trauma can be initiated through several mechanisms including chronic aberrant loading of the joint as in the case of anterior cruciate ligament tear (ACLt). Chronic aberrant loading of joint surfaces leads to chondrocyte apoptosis, necrosis, release of inflammatory mediators that lead to enhanced matrix degradation, and suppression of collagen and proteoglycan synthesis.
We hypothesize that rabbits undergoing ACLt will have increased gross and microscopic cartilage damage, increased subchondral bone remodeling, increased osteophyte formation, elevated expression of inflammatory and catabolism markers, and decreased anabolism markers. We also hypothesize that pharmacological inhibition of CAMKK2 will attenuate PTOA severity.
Methods: New Zealand White Rabbits underwent ACLt of the right knee and then were treated either with saline or STO-609, a CAMKK2 inhibitor, three times per week for four months. Left and right knees were harvested and preserved for either microCT analysis or RNA isolation and analysis using qRT-PCR.
Results/Findings: Preliminary PCR results show increased levels of Col2a1 and Acan in the STO-609 group compared to saline. However, IL-6 and MMP-13 were also elevated in the STO-609 group. Micro CT analysis was used to evaluate total volume of osteophytes, cross-sectional thickness of the right medial tibial plateau, and the bone volume to tissue volume ratio of the subchondral plate. While none of the results are statistically significant, more samples need to be analyzed.
Conclusions/Discussion: None of the current data shows statistical differences between the analyzed groups. However, there are more samples that need to be analyzed, and PTOA progression timepoint may be influencing these results.
Translational/Human Health Impact: If this drug shows attenuation of PTOA, it could help future patients after traumatic injury.