Brigitte Jolles-Haeberli

Pathogenic role of basic calcium phosphate crystals in destructive arthropathies.

Background basic calcium phosphate (BCP) crystals are commonly found in osteoarthritis (OA) and are associated with cartilage destruction. BCP crystals induce in vitro catabolic responses with the production of metalloproteases and inflammatory cytokines such as interleukin-1 (IL-1). In vivo, IL-1 production induced by BCP crystals is both dependant and independent of NLRP3 inflammasome. We aimed to clarify 1/ the role of BCP crystals in cartilage destruction and 2/ the role of IL-1 and NLRP3 inflammasome in cartilage degradation related to BCP crystals. Methodology/ Principal Findings synovial membranes isolated from OA knees were analysed by alizarin Red and FTIR. Pyrogen free BCP crystals were injected into right knees of WT, NLRP3 -/-, ASC -/-, IL-1α -/- and IL-1β-/- mice and PBS was injected into left knees. To assess the role of IL-1, WT mice were treated by intra-peritoneal injections of anakinra, the IL-1Ra recombinant protein, or PBS. Articular destruction was studied at d4, d17 and d30 assessing synovial inflammation, proteoglycan loss and chondrocyte apoptosis. BCP crystals were frequently found in OA synovial membranes including low grade OA. BCP crystals injected into murine knee joints provoked synovial inflammation characterized by synovial macrophage infiltration that persisted at day 30, cartilage degradation as evidenced by loss of proteoglycan staining by Safranin-O and concomitant expression of VDIPEN epitopes, and increased chondrocyte apoptosis. BCP crystal-induced synovitis was totally independent of IL-1α and IL-1β signalling and no alterations of inflammation were observed in mice deficient for components of the NLRP3-inflammasome, IL-1α or IL-1β. Similarly, treatment with anakinra did not prevent BCP crystal effects. In vitro, BCP crystals elicited enhanced transcription of matrix degrading and pro-inflammatory genes in macrophages. Conclusions/ Significance intra-articular BCP crystals can elicit synovial inflammation and cartilage degradation suggesting that BCP crystals have a direct pathogenic role in OA. The effects are independent of IL-1 and NLRP3 inflammasome.

A patient-specific model of total knee arthroplasty to estimate patellar strain: A case study

BACKGROUND Inappropriate patellar cut during total knee arthroplasty can lead to patellar complications due to increased bone strain. In this study, we evaluated patellar bone strain of a patient who had a deeper patellar cut than the recommended. METHODS A patient-specific model based on patient preoperative data was created. The model was decoupled into two levels: knee and patella. The knee model predicted kinematics and forces on the patella during squat movement. The patella model used these values to predict bone strain after total knee arthroplasty. Mechanical properties of the patellar bone were identified with micro-finite element modeling testing of cadaveric samples. The model was validated with a robotic knee simulator and postoperative X-rays. For this patient, we compared the deeper patellar cut depth to the recommended one, and evaluated patellar bone volume with octahedral shear strain above 1%. FINDINGS Model predictions were consistent with experimental measurements of the robotic knee simulator and postoperative X-rays. Compared to the recommended cut, the deeper cut increased the critical strain bone volume, but by less than 3% of total patellar volume. INTERPRETATION We thus conclude that the predicted increase in patellar strain should be within an acceptable range, since this patient had no complaints 8 months after surgery. This validated patient-specific model will later be used to address other questions on groups of patients, to eventually improve surgical planning and outcome of total knee arthroplasty.