ABSTRACT
OBJECTIVES: Anterior cruciate ligament (ACL) reconstruction after injury does not prevent post-traumatic osteoarthritis (PTOA). Circulating microRNA (miRNA) and metabolite changes emerging shortly after ACL injury and reconstruction remain insufficiently defined, potentially harbouring early cues contributing to PTOA evolution. Moreover, their differential expression between females and males also may influence PTOA's natural trajectory. This study aims to determine alterations in plasma miRNA and metabolite levels in the early stages following ACL reconstruction and between females and males. METHODS: A cohort of 43 ACL reconstruction patients was examined. Plasma was obtained at baseline, 2-weeks, and 6-weeks post-surgery (129 biospecimens in total). High throughput miRNA sequencing and metabolomics were conducted. Differentially expressed miRNAs and metabolites were identified using negative binomial and linear regression models, respectively. Associations between miRNAs and metabolites were explored using time and sex as co-variants, (pre- versus 2- and 6-weeks post-surgery). Using computational biology, miRNA-metabolite-gene interaction and pathway analyses were performed. RESULTS: Levels of 46 miRNAs were increased at 2-weeks post-surgery compared to pre-surgery (baseline) using miRNA sequencing. Levels of 13 metabolites were significantly increased while levels of 6 metabolites were significantly decreased at 2-weeks compared to baseline using metabolomics. Hsa-miR-145-5p levels were increased in female subjects at both 2-weeks (log2-fold-change 0.71, 95%CI 0.22,1.20) and 6-weeks (log2-fold-change 0.75, 95%CI 0.07,1.43) post-surgery compared to males. In addition, hsa-miR-497-5p showed increased levels in females at 2-weeks (log2-fold-change 0.77, 95%CI 0.06,1.48) and hsa-miR-143-5p at 6-weeks (log2-fold-change 0.83, 95%CI 0.07,1.59). Five metabolites were decreased at 2-weeks post-surgery in females compared to males: L-leucine (-1.44, 95%CI -1.75,-1.13), g-guanidinobutyrate (-1.27, 95%CI 1.54,-0.99), creatinine (-1.17, 95%CI -1.44,-0.90), 2-methylbutyrylcarnitine (-1.76, 95%CI -2.17,-1.35), and leu-pro (-1.13, 95%CI -1.44,-0.83). MiRNA-metabolite-gene interaction analysis revealed key signalling pathways based on post-surgical time-point and in females versus males. CONCLUSION: MiRNA and metabolite profiles were modified by time and by sex early after ACL reconstruction surgery, which could influence surgical response and ultimately risk of developing PTOA.
ABSTRACT
BACKGROUND: We set out to investigate whether anterior knee pain following anterior cruciate ligament reconstruction has a significant effect on patients, and whether it should influence graft choice. METHODS: This was a qualitative analysis of a set of recreational athletes treated at a university hospital at about 1 year following anterior cruciate ligament reconstruction surgery. Participants were interviewed by an orthopaedic fellow and resident using structured, open-ended questions. Inductive theme analysis was used to code the data. RESULTS: There were 4 major themes: (1) Our hypothesis was that patients would be given adequate information to make an appropriate graft choice. This hypothesis was rejected. Discussion took place, but with little details or rationale for the graft choice. The predominant theme was that the surgeon made the decision, and there was a lack of reliable information for the patient to make a choice. (2) The overall theme was that most patients had no anterior knee pain, and it did not interfere with activities of daily living. (3) One theme was that patients were able to resume all sports without restriction, but in some, the anterior knee pain interfered with the more demanding activities such as impact, cutting, and pivoting. A separate theme was that fear was a major impediment to return to sports and was not related to the anterior knee pain. (4) The overriding theme was that the generalized closures associated with the COVID-19 pandemic slowed the rehabilitation process. Although virtual care was available in general, it was not particularly satisfactory. Patients indicated that they had not been able to return to the gym or to their sporting activities as a result. CONCLUSIONS: Amongst non-competitive athletes, anterior knee pain post-anterior cruciate ligament reconstruction surgery does not significantly affect activities of daily living. Although there is a minor effect on sporting activities, the inability to return to sports is related to factors such as the COVID-19 pandemic, fear, or insufficient rehabilitation, rather than anterior knee pain. Overall, anterior knee pain is not a significant factor that plays a role in determining graft choice.
