Premium
Blocking the receptor for advanced glycation end‐products but not Toll‐like receptor 4 attenuates the progression of OA (835.13)
Author(s) -
Wilhelm Spencer,
Mecham David,
Chavez Matias Elizabeth,
Kartchner Jeff,
Crepeau Philip,
Andersen Karl,
Vandruff James,
Robinson MarLeice,
Christensen Ian,
Taylor Kara,
Reynolds Paul,
Kooyman David
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.835.13
Subject(s) - rage (emotion) , glycation , receptor , osteoarthritis , hmgb1 , medicine , toll like receptor , chemistry , pharmacology , immunology , biology , pathology , neuroscience , innate immune system , alternative medicine
Receptors for Advanced Glycation End Products (RAGE) and Toll Like Receptor 4 (TLR‐4) have been shown to play a role in the development of Osteoarthritis (OA). We have previously shown that knocking out RAGE in mice slows the disease progression in articular cartilage of the knee. The objective of this study was to determine if application of the compound TAK‐242, a TLR‐4 specific inhibitor, in conjunction with knocking out RAGE could further attenuate the disease. Destabilization of the medial meniscus of RAGE KO and Wild Type (WT mice) was performed, and severity of OA was qualitatively analyzed through two standardized scoring systems (Mankin and OARSI). We also performed immunohistochemistry to analyze levels of HtrA1 and TGF‐β1, known biomarkers for the disease. Surprisingly, addition of the TLR blocker disrupted the protection afforded by knocking out RAGE, and its application to WT mice had no protective effect. We conclude that while blockage of the RAGE pathway alone is beneficial to the attenuation of OA, hampering the TLR‐4 pathway offers no protective benefits. We hypothesize that blocking TLR‐4 receptor mitigates the beneficial effects of knocking out RAGE on OA.