Amentadione from the Alga Cystoseira usneoides as a Novel Osteoarthritis Protective Agent in an Ex Vivo Co-Culture OA Model.

Osteoarthritis (OA) remains a prevalent chronic disease without effective prevention and treatment. Amentadione (YP), a meroditerpenoid purified from the alga Cystoseira usneoides, has demonstrated anti-inflammatory activity. Here, we investigated the YP anti-osteoarthritic potential, by using a novel OA preclinical drug development pipeline designed to evaluate the anti-inflammatory and anti-mineralizing activities of potential OA-protective compounds. The workflow was based on in vitro primary cell cultures followed by human cartilage explants assays and a new OA co-culture model, combining cartilage explants with synoviocytes under interleukin-1ß (IL-1ß) or hydroxyapatite (HAP) stimulation. A combination of gene expression analysis and measurement of inflammatory mediators showed that the proposed model mimicked early disease stages, while YP counteracted inflammatory responses by downregulation of COX-2 and IL-6, improved cartilage homeostasis by downregulation of MMP3 and the chondrocytes hypertrophic differentiation factors Col10 and Runx2. Importantly, YP downregulated NF-κB gene expression and decreased phosphorylated IkBα/total IkBα ratio in chondrocytes. These results indicate the co-culture as a relevant pre-clinical OA model, and strongly suggest YP as a cartilage protective factor by inhibiting inflammatory, mineralizing, catabolic and differentiation processes during OA development, through inhibition of NF-κB signaling pathways, with high therapeutic potential.

Benefits of Tranexamic Acid in Total Knee Arthroplasty: A Classification and Regression Tree Analysis in Function of Instrumentation, BMI, and Gender.

Tranexamic acid (TXA) is an antifibrinolytic drug that reduces blood loss in patients that undergo Total knee arthroplasty (TKA). Few studies compare its effect on conventional instrumentation (CI) versus patient-specific instrumentation (PSI). The main objective of this study was to understand analytically how TXA usage in both instrumentations influenced blood loss in TKA differently and see if the differences seen could be explained by the patient's body mass index (BMI) and gender. This nonrandomized retrospective study sample consisted of 688 TKA procedures performed on patients who had symptomatic arthrosis resistant to conservative treatment. Descriptive analysis was used to evaluate blood loss using hemoglobin (Hb) mean values and mean variation (%). The Classification and Regression Tree (CRT) method was applied to understand how the independent variables affected the dependent variable. Comparing patients submitted to the same instrumentation, where some received TXA and others did not, patients that received TXA had lower blood loss. Comparing patients who underwent TKA with different instrumentations and without the use of TXA, it was found that patients who underwent TKA with PSI had lower blood loss than those who underwent TKA with CI. However, when these same instruments were compared again, but associated with the use of TXA, the opposite was true with patients undergoing TKA with PSI showing greater blood loss than patients undergoing TKA with CI. TXA usage in TKA is significantly beneficial in minimizing blood loss and regardless of instrumentation. When using TXA, the lowest blood loss was obtained in patients with higher BMI and submitted to TKA with CI. This is most likely explained by the synergistic antifibrotic effect of TXA with adipokines, such as plasminogen activator inhibitor-1 (PAI-1), found in the femoral bone marrow which is perforated using CI. If, however, TXA wasn't used, the lowest blood loss was obtained in patients submitted to TKA with PSI.