Cellular and molecular landscapes of inflammation in anterior cruciate ligament rupture patients are independent on concurrent meniscal injury

Background Anterior cruciate ligament (ACL) rupture greatly increases the risk of developing knee osteoarthritis (OA), especially when accompanied by meniscal injury. Therefore, we examined biological processes in the knee joint of ACL rupture patients with or without concurrent meniscal injury. The aim of this study was to explore whether concurrent meniscal injury leads to distinct inflammatory cellular or molecular landscapes and patient reported outcome measures (PROMs), like knee function and pain, compared to an isolated ACL rupture with intact menisci. Methods Synovium, synovial fluid and blood of 24 patients with an ACL rupture were collected at the day of ACL reconstruction surgery. Inflammation was scored in H&E-stained synovium biopsies. Cellular composition of synovium, synovial fluid and blood was determined using flow cytometry. Synovial gene expression was measured with bulk RNA sequencing. Luciferase reporter assays using SW1353 cells were used to determine signalling pathway activation in response to serum and synovial fluid. Patients completed the KOOS questionnaire preoperatively and six months and two years postoperatively, and the EQ-5D questionnaire preoperatively and two years postoperatively. Results There was heterogeneity in synovitis among patients, but no significant differences were found between patients with an isolated ACL rupture and those with concurrent meniscal injury in terms of synovial inflammation scores, cellular composition, synovial gene expression, or pathway activation induced by serum or synovial fluid. Moreover, meniscal status did not affect PROM scores at time of ACL reconstruction. PROM scores showed generally better outcomes six months and two years postoperatively, with patients with concurrent meniscal injury showing subtly less improvement. Conclusion The presence of concurrent meniscal injury did not influence cellular and molecular landscapes of inflammation and minimally affected patient reported outcome measures up to two years following anterior cruciate ligament reconstruction.