Post-traumatic osteoarthritis has a distinct temporal pattern of synovial inflammatory cell infiltration, stimulated by aggrecan degradation by ADAMTS. — The Association Specialists

Post-traumatic osteoarthritis has a distinct temporal pattern of synovial inflammatory cell infiltration, stimulated by aggrecan degradation by ADAMTS. (282)

Miriam Jackson 1 , Babak Moradi 2 , Susan Smith 1 , Christopher Little 1
  1. Kolling Institute of Medical Research, St Leonards, NSW, Australia
  2. Orthopaedic Clinic, University of Heidelberg, Heidelberg, Germany

Introduction: There is emerging evidence that increased synovial inflammatory cells may play an active role in osteoarthritis (OA) initiation and progression. Here we define the temporal pattern of inflammatory cells in synovium after OA-inducing and non-inducing (Sham) surgery. Additionally, we have used Jaffa mice, which have aggrecan resistant to ADAMTS cleavage and are chondro-protected in this surgical model, to understand what factors may drive the inflammatory response. Methods: Destabilization of the medial meniscus (DMM) and sham surgery was performed on ten-week-old male C57BL6 (WT) and Jaffa mice. At sacrifice (day 1, 3 and intervals up to 16 weeks post-surgery) knee joint synovial membrane (SM) were harvested, inflammatory cells isolated and quantifiedby FACS (n = 4). Results: Peaks in both CD4+ and CD8+ T-cells were seen at week 2 and 5 in WT SM with levels remaining elevated thereafter in DMM but not Sham. Activated macrophages rapidly increased and then returned to control levels by 5 weeks in WT DMM and Sham. Levels of M1 cells were increased immediately (day 1) but decreased dramatically at day 3 followed by a smaller peak at day 21 before decreasing in both DMM and Sham. Peaks in M2 cells were seen over time (day 3, 14, 28, 56, 84) in WT DMM and Sham. Jaffa DMM SM had lower numbers of CD4+ and CD8+ lymphocytes but similar levels of activated macrophages as WT DMM. The percentage of M1 cells in Jaffa SM decreased less dramatically and remained higher than WT DMM until day 28, and interestingly, little to no M2 cells were evident in Jaffa SM. Conclusion: Distinct phases of synovial inflammation occur after joint trauma and Jaffa mice have an altered pattern of inflammation suggesting lack of cleavage of aggrecan by ADAMTS and/or downstream consequences of this inhibits post-traumatic inflammatory response.