¹Julius Wolff Institute (JWI), Charité, Charité Universitätsmedizin Berlin, Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Deutschland
²Center for Musculoskeletal Surgery, Charité Universitätsmedizin Berlin, Berlin, Deutschland

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Objectives and questions: Osteoarthritis (OA) is a degenerative joint disease affecting over 590 million patients globally, characterized by decreased mobility and increased joint pain due to cartilage deterioration and chronic inflammation. Typically, OA is a disease that progresses over time due to several risk factors. Unresolved joint-trauma results in post-traumatic osteoarthritis (PTOA) and is of interest as it can be traced to an instance of joint trauma that results in development of OA. Neutrophils are considered the first trauma-responders in innate immunity, recognizing tissue damage to produce reactive oxygen species, aid in clearance and trigger downstream immune cascades [1]. It has been shown that oxidative stress and elevated neutrophil levels are present in the synovial environment of OA patients [2], [3]. However, the regulatory role of the early neutrophil response and the initiation of PTOA is not clearly understood. Consequently, we aimed to characterize the role of the innate immune response and oxidative stress in PTOA initiation.

Material and methods: We performed flow cytometry analysis to immunophenotype neutrophils from peripheral blood, synovial drainage fluid, and synovial fluid from patients undergoing surgical interventions for a range of surgical joint interventions with a known association with PTOA development. Surgical interventions included ACL reconstruction and autologous chondrocyte transfer. Samples were received 24 hours before surgery, during surgery, and 24- and 6-weeks post surgery. Markers for analysis includes Neutrophil lineage markers (CD15/16) and Markers relevant in classifying inactivated Neutrophils (CD62L) and activated Neutrophils (CD66b/11b).

Results: Data analysis confirmed changes in markers relevant for neutrophil activation status in samples prior- and post-surgical intervention. Specifically, post- surgical intervention samples of peripheral blood, drainage, and synovial fluid showed elevated amounts of activated neutrophils, indicating the impact of trauma-level to the activation of the innate immune response. In some cases, the activated neutrophil presence was observed in synovial fluid samples at the 6-week follow-up.

Discussion and conclusions: The results indicate persistence in the presence of Neutrophils in the activated phenotype, suggesting the role that Neutrophils can play in the development of PTOA. Elucidating the role of initial neutrophil response to intervention surgery may aid in patient stratification modelling and further indicate potential therapeutic targets.

References

[1] Mehrani Y, Rahimi Junqani R, Morovati S, Mehrani H, Karimi N, Ghasemi S. The Importance of Neutrophils in Osteoarthritis: Current Concepts and Therapeutic Perspectives. Immuno. 2023;3(3):250-72. DOI: 10.3390/immuno3030017
[2] Lepetsos P, Papavassiliou AG. ROS/oxidative stress signaling in osteoarthritis. Biochim Biophys Acta. 2016 Apr;1862(4):576-91. DOI: 10.1016/j.bbadis.2016.01.003
[3] Wang G, Jing W, Bi Y, Li Y, Ma L, Yang H, Zhang Y. Neutrophil Elastase Induces Chondrocyte Apoptosis and Facilitates the Occurrence of Osteoarthritis via Caspase Signaling Pathway. Front Pharmacol. 2021 Apr 14;12:666162. DOI: 10.3389/fphar.2021.666162