Temporal profiling of lipid mediators in synovium and tibial plateau during joint inflammation in a collagenase-induced mouse model of osteoarthritis

Abstract

Objective: Inflammatory mediators, including polyunsaturated fatty acids (PUFAs) and oxylipins, play critical roles in osteoarthritis (OA) development. We aimed to map the time-dependent profile of lipid mediators in synovium and tibial plateau associated with joint inflammation in a mouse model of OA.

Methods: OA was induced by intra-articular collagenase injection in the knee of 8-week-old male mice, with the contralateral knee injected with phosphate-buffered saline (PBS) serving as the control. Over 31 days post-injection, knee swelling was measured (n = 4 per time point, repeated measures), and joint tissues were harvested for histological and immunohistochemical analyses (n = 3-4 per time point), with data analyzed using linear mixed-effects models. On days 1, 3, 7, and 21 after OA induction, synovium and tibial plateau tissues were collected for targeted lipidomic profiling (n = 3-4 per time point).

Results: We identified days 1, 3, 7, and 21 as key time points associated with markers of joint inflammation, including knee swelling, synovial neutrophil and macrophage infiltration, and synovial fibrosis. Hierarchical clustering revealed eight main patterns in PUFA and oxylipin profiles in the synovium over this time course. Further investigation into the changes suggested specific links to the biosynthetic pathways of oxylipins. Additionally, temporal changes in PUFA and oxylipin levels were noted in tibial plateau. Conclusion: Our study provides a temporal map of PUFA and oxylipin dynamics in joint tissues during progression of OA inflammation, highlighting tissue-specific inflammatory profiles, and offering insights into lipid mediator involvement in OA pathogenesis.