OP0152 Synovial Macrophages Promote TGF-β Signaling After Intra-Articular Injections of Oxidized LDL in Naïve Murine Knee Joints, Preventing Production of Pro-Inflammatory Factors S100A8/9, Chemokines and Aggrecanase-Induced Neo-Epitopes

BackgroundIn previous studies we found that synovial macrophages regulate joint pathology during experimental inflammatory osteoarthritis (OA) and that high systemic levels of Low density lipoproteins (LDL) aggravate OA joint pathology.[1-4] LDL in inflamed synovium is prone to be oxidized (oxLDL) and taken-up by macrophages, leading to an activated phenotype.[5]ObjectivesIn this study, we investigate whether direct injection of oxLDL into a murine knee joint induces pathology and elucidate the role of synovial macrophages in that process.MethodsKnee joints of C57BL/6 mice were injected five consecutive days with 1.2 mg/mL oxLDL, LDL, or an equal volume of vehicle (PBS). This same procedure was performed in mice depleted of synovial macrophages by intra-articular injection of clodronate liposomes seven days prior to the consecutive injections. Joint pathology was investigated by immunohistochemistry and RNA expression and protein production by synovium were determined using RT-PCR and luminex, respectively. TGF-β activity was measured using a functional CAGA-luciferase assay. Data are depicted as mean ± standard deviation.ResultsLDL and oxLDL injection in naïve knee joints did neither increase synovial thickening, nor production of pro-inflammatory factors (IL-1β, IL-6 and S100A8/9) compared to vehicle injection. TGF-β activity in synovial wash-outs was, however, significantly increased by 33% (from 84.7 ng/mL/g synovium ±14.4 to 113.0 ng/mL/g synovium ±33.3; p