کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6125512 1220179 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Depletion of gangliosides enhances cartilage degradation in mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی ایمونولوژی، آلرژی و روماتولوژی
پیش نمایش صفحه اول مقاله
Depletion of gangliosides enhances cartilage degradation in mice
چکیده انگلیسی

SummaryObjectiveGlycosphingolipids (GSLs) are ubiquitous membrane components that play a functional role in maintaining chondrocyte homeostasis. We investigated the potential role of gangliosides, one of the major components of GSLs, in osteoarthritis (OA) pathogenesis.DesignBoth age-associated and instability-induced OA models were generated using GM3 synthase knockout (GM3S−/−) mice. A cartilage degradation model and transiently GM3S-transfected chondrocytes were analyzed to evaluate the function of gangliosides in OA development. The amount of each series of GSLs in chondrocytes after IL-1α stimulation was profiled using mass spectrometry (MS).ResultsOA changes in GM3S−/− mice were dramatically enhanced with aging compared to those in wild-type (WT) mice. GM3S−/− mice showed more severe instability-induced pathologic OA in vivo. Ganglioside deficiency also led to the induction of matrix metalloproteinase (MMP)-13 and ADAMTS-5 secretion and chondrocyte apoptosis in vitro. In contrast, transient GM3S transfection of chondrocytes suppressed MMP-13 and ADAMTS-5 expression after interleukin (IL)-1α stimulation. GSL profiling revealed the presence of abundant gangliosides in chondrocytes after IL-1α stimulation.ConclusionGangliosides play a critical role in OA pathogenesis by regulating the expression of MMP-13 and ADAMTS-5 and chondrocyte apoptosis. Based on the obtained results, we propose that gangliosides are potential target molecules for the development of novel OA treatments.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Osteoarthritis and Cartilage - Volume 22, Issue 2, February 2014, Pages 313-322
نویسندگان
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