Docosahexenoic acid treatment ameliorates cartilage degeneration via a p38 MAPK-dependent mechanism.

Osteoarthritis (OA) is a common chronic inflammatory disease, characterized by cartilage degradation. The aberrant expression of matrix metalloproteinase-13 (MMP-13) plays a vital role in the pathogenesis of OA. The anti­inflammatory property of docosahexenoic acid (DHA) was previously revealed and showed that DHA retards the progress of many types of inflammatory disease. To evaluate the prophylactic function of DHA in OA, the effect of DHA on cartilage degeneration was assessed in interleukin­1ß (IL­1ß) stimulated human chondrosarcoma SW1353 cells or a rat model of adjuvant­induced arthritis (AIA). The safe concentration range (0­50 µg/ml in vitro) of DHA was determined by flow cytometry and MTT assay. The inhibitory effects of DHA on MMP­13 mRNA and protein expression were confirmed by RT­qPCR, ELISA and western blotting. Furthermore, findings of an in vivo study showed that DHA can increase the thickness of articular cartilage and decrease MMP­13 expression in cartilage matrix in a rat AIA model. We also revealed the mechanism by which DHA ameliorates cartilage degeneration from OA. The DHA-mediated inhibition of MMP­13 expression was partially attributed to the inactivation of the p38 mitogen­activated protein kinases pathway by suppressing p­p38 in IL-1ß-stimulated SW1353 cells and a rat AIA model. Our findings suggested that DHA is a promising therapeutic agent that may be used for the prevention and treatment of OA.

Abnormal expression and distribution of heat shock protein 90: potential etiologic immunoendocrine mechanism of glucocorticoid resistance in idiopathic nephrotic syndrome.

Resistance to glucocorticoid (GC) treatment in some patients with idiopathic nephrotic syndrome (INS) is a significant clinical problem. Heat shock protein 90 (HSP90) is the chaperon protein of the GC receptor, which is supposed to be the key factor of GC response. Therefore, we conducted this study to define the mechanisms of GC resistance related to HSP90. INS patients and cell lines with differing GC responses were included in the present study. We found that the level of HSP90 mRNA expression in INS patients was significantly higher than that in healthy controls and that HSP90 expression in GC-resistant INS patients was higher than that in GC-sensitive INS patients. A confocal immunofluorescence test was performed to investigate the subcellular localization of HSP90, and we found that the distribution of HSP90 in the GC-resistant INS group was greater in the nuclei than that of the GC-sensitive INS group. When the function of HSP90 was blocked by the HSP90-specific inhibitor, the GC sensitivity of GC-sensitive cells decreased remarkably. These results indicate that HSP90 plays a vital role in GC response. In addition, the abnormality in the mRNA level and subcellular distribution of HSP90 in GC-resistant INS patients may be etiologically significant in terms of endogenous/synthetic GC resistance. On one hand, it may disturb immunoendocrine regulation via endogenous GC and immune homeostasis and thus be involved in the occurrence of the immune-mediated disease; on the other hand, it may influence the patient's response to synthetic GC treatment and result in treatment failure.