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  • Barreto, Goncalo; Manninen, Mikko; Eklund, Kari K. (2020)
    Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. In particular, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by alarmins (also known as danger signals) are thought to be involved. Thus, toll-like receptors (TLRs) and their signaling pathways are of particular interest. Recent reports suggest that among the TLR-induced innate immune responses, apoptosis is one of the critical events. Apoptosis is of particular importance, given that chondrocyte death is a dominant feature in OA. This review focuses on the role of TLR signaling in chondrocytes and the role of TLR activation in chondrocyte apoptosis. The functional relevance of TLR and TLR-triggered apoptosis in OA are discussed as well as their relevance as candidates for novel disease-modifying OA drugs (DMOADs).
  • Svard, Tuomas; Lakovaara, Martti; Pakarinen, Harri; Haapea, Marianne; Kiviranta, Ilkka; Lammentausta, Eveliina; Jurvelin, Jukka; Tervonen, Osmo; Ojala, Risto; Nieminen, Miika (2018)
    Objective. To investigate the association of cartilage defect severity, as determined by the International Cartilage Repair Society (ICRS) grading with indentation stiffness and T2 relaxation time of magnetic resonance imaging (MRI), a biomarker for the integrity of articular cartilage. Design. Twenty-one patients scheduled for arthroscopic were included in the study. Prior to arthroscopy, subjects underwent quantitative MRI of articular cartilage, namely T2 relaxation time mapping at 1.5 T. Within 2 months, subjects underwent arthroscopy, which also included ICRS grading and measurement of arthroscopic indentation stiffness. Arthroscopic evaluations and T2 mapping at anterior, central, and posterior medial and lateral femoral condyles were correlated using a colocalization scheme. Differences in Young's modulus, as derived by indentation tests, and T2 times between ICRS grades were analyzed using Mann-Whitney's U or Kruskal-Wallis H tests. The correlation between modulus and T2 times was analyzed using Spearman's rank correlation coefficients. Results. Modulus and T2 showed significant topographical variation. In the anterior region of interest (ROI) on the medial condyle the modulus showed a negative association with ICRS grade (P = 0.040) and the T2 times were longer in ICRS grade 2 compared with grades 0 and 1 (P = 0.047). Similar, but nonsignificant associations were found in the central ROI on the medial condyle. No significant correlations were observed between the indentation modulus and T2 times. Conclusions. Cartilage degeneration is identified both with mechanical indentation and T2 mapping in MRI. However, in this study, indentation stiffness and T2 relaxation time in vivo, were not associated.
  • Sillat, Tarvo; Barreto, Goncalo; Clarijs, Paul; Soininen, Antti; Ainola, Mari; Pajarinen, Jukka; Korhonen, Matti; Konttinen, Yrjo; Sakalyte, Regina; Hukkanen, Mika; Ylinen, Pekka; Nordstrom, Dan (2013)