OBJECTIVE: Autophagy, a key homeostasis mechanism, is defective in @entity571 ( @entity571 ) and @entity2175 ( @entity2175 ). @entity2175 has been proposed as a risk factor for @entity571 . We hypothesized that @entity6 impairs articular cartilage integrity by decreasing autophagy. Our objective was to investigate the effects of high @entity413 and @entity2690 , characteristics of @entity2175 , on cartilage homeostasis. METHODS: Immortalized @entity1 chondrocytes (TC28a2) and primary @entity1 chondrocytes (HC) were cultured in 25  mM or 0  mM @entity413 and treated with @entity2690 (10, 100, 500  nM) for 2, 6 or 24  h. Activity of @entity21684 -II, @entity584 and @entity19172 was evaluated by Western blotting (WB). @entity1 cartilage explants were cultivated with 25  mM @entity413 and @entity2690 (100,1000  nM) for 24  h to evaluate histopathology. @entity1550 and @entity1356 expression was determined by immunohistochemistry and WB. Effects of @entity3446 (10   M) were analyzed by WB. @entity21684 and @entity19172 expression was determined by WB in chondrocytes from Healthy, Non @entity6 and @entity6 @entity1 . RESULTS: @entity2690 downregulates autophagy by reducing @entity21684 II expression and increasing @entity584 and @entity19172 phosphorylation. Loss of proteoglycans and increased @entity1550 and @entity1356 expression was observed after @entity2690 treatment. Autophagy activation by @entity3446 reversed @entity2690 effects. Importantly, chondrocytes from @entity6 @entity1 showed decreased @entity21684 and increased p- @entity19172 expression compared to Healthy and Non-Diabetic @entity571 @entity1 . CONCLUSIONS: These results suggest that decreased autophagy might be a mechanism by which @entity6 influences cartilage degradation. Pharmacological activation of autophagy may be an effective therapeutic approach to prevent @entity2175 -induced @entity16 .

XXXX decreases autophagy and leads to cartilage degradation.

@entity2175 :: ('MESH:D003924', 'Disease') :: ['T2D', 'Type 2 Diabetes'] @entity1 :: ('9606', 'Species') :: ['human', 'Human', 'patients'] @entity571 :: ('MESH:D010003', 'Disease') :: ['Osteoarthritis', 'OA'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic-OA', 'Diabetic-OA', 'diabetes'] @entity19172 :: ('6194', 'Gene') :: ['rpS6'] @entity1356 :: ('3553', 'Gene') :: ['IL-1b'] @entity16 :: ('MESH:D009422', 'Disease') :: ['cartilage damage'] @entity2690 :: ('3630', 'Gene') :: ['insulin', 'Insulin'] @entity584 :: ('207', 'Gene') :: ['Akt'] @entity1550 :: ('4322', 'Gene') :: ['MMP-13'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['Rapamycin', 'rapamycin'] @entity21684 :: ('84557', 'Gene') :: ['LC3'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity2690 :: (3630,Gene) :: ['Insulin']
