- 作者：F. Sasazawa ; T. Onodera ; T. Yamashita ; N. Seito ; Y. Tsukuda ; N. Fujitani ; Y. Shinohara ; N. Iwasaki
- 关键词：Osteoarthritis ; Mice ; Gangliosides ; Glycosphingolipids ; Interleukin-1伪
- 刊名：Osteoarthritis and Cartilage
- 出版年：February, 2014
- 年：2014
- 卷：22
- 期：2
- 页码：313-322
- 全文大小：1524 K
Summary
Objective
Glycosphingolipids (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.Design
Both age-associated and instability-induced OA models were generated using GM3 synthase knockout (GM3S鈭?鈭?/em>) 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-1伪 stimulation was profiled using mass spectrometry (MS).
Results
OA changes in GM3S鈭?鈭?/em> mice were dramatically enhanced with aging compared to those in wild-type (WT) mice. GM3S鈭?鈭?/em> mice showed more severe instability-induced pathologic OA in聽vivo. Ganglioside deficiency also led to the induction of matrix metalloproteinase (MMP)-13 and ADAMTS-5 secretion and chondrocyte apoptosis in聽vitro. In contrast, transient GM3S transfection of chondrocytes suppressed MMP-13 and ADAMTS-5 expression after interleukin (IL)-1伪 stimulation. GSL profiling revealed the presence of abundant gangliosides in chondrocytes after IL-1伪 stimulation.
Conclusion
Gangliosides 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.