期刊
JOINT BONE SPINE
卷 81, 期 4, 页码 320-324出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.jbspin.2014.01.018
关键词
MyD88; TLRs; Experimental osteoarthritis; Cartilage degradation and metabolism; Synovial inflammation; Chondrocytes apoptosis
类别
资金
- Fonds National Suisse de la recherche scientifique [310030-130085/1]
- Fondation Jean- and Linette-Warnery
- Fondation pour la Recherche Medicale (FRM)
- Association pour la Recherche en Pathologie Synoviale (ARPS)
- Association Rhumatisme et Travail (ART)
- Institute for Arthritis Research (JAR)
- Swiss National Science Foundation (SNF) [310030_130085] Funding Source: Swiss National Science Foundation (SNF)
Objectives: The aim of our study was to evaluate the role of cell-membrane expressed TLRs and the signaling molecule MyD88 in a murine model of OA induced by knee menisectomy (surgical partial removal of the medial meniscus [MNX]). Methods: OA was induced in 8-10 weeks old C57Bl/6 wild-type (WT) female (n = 7) mice and in knockout (KO) TLR-1 (n = 7), -2 (n = 8), -4 (n = 9) -6 (n = 5), MyD88 (n = 8) mice by medial menisectomy, using the sham-operated contralateral knee as a control. Cartilage destruction and synovial inflammation were evaluated by knee joint histology using the OARSI scoring method. Apoptotic chondrocytes and cartilage metabolism (collagen II synthesis and MMP-mediated aggrecan degradation) were analyzed using immunohistochemistry. Results: Operated knees exhibited OA features at 8 weeks post-surgery compared to sham-operated ones. In menisectomized TLR-1, -2, -4, and -6 deficient mice, cartilage lesions, synovial inflammation and cartilage metabolism were similar to that in operated WT mice. Accordingly, using the same approach, we found no significant protection in MyD88-deficient mice in terms of OA progression as compared to WT littermates. Conclusions: Deficiency of TLRs or their signalling molecule MyD88 did not impact on the severity of experimental OA. Our results demonstrate that MyD88-dependent TLRs are not involved in this murine OA model. Moreover, the dispensable role of MyD88, which is also an adaptor for IL-1 receptor signaling, suggests that IL-1 is not a key mediator in the development of OA. This latter hypothesis is strengthened by the lack of efficiency of IL-1 beta antagonist in the treatment of OA. (C) 2014 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
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