Insulin decreases autophagy and leads to cartilage degradation.
Osteoarthritis Cartilage
; 24(4): 731-9, 2016 Apr.
Article
in En
| MEDLINE
| ID: mdl-26549531
ABSTRACT
OBJECTIVE:
Autophagy, a key homeostasis mechanism, is defective in Osteoarthritis (OA) and Type 2 Diabetes (T2D). T2D has been proposed as a risk factor for OA. We hypothesized that diabetes impairs articular cartilage integrity by decreasing autophagy. Our objective was to investigate the effects of high glucose and insulin, characteristics of T2D, on cartilage homeostasis.METHODS:
Immortalized human chondrocytes (TC28a2) and primary human chondrocytes (HC) were cultured in 25 mM or 0 mM glucose and treated with insulin (10, 100, 500 nM) for 2, 6 or 24 h. Activity of LC3-II, Akt and rpS6 was evaluated by Western blotting (WB). Human cartilage explants were cultivated with 25 mM glucose and insulin (100,1000 nM) for 24 h to evaluate histopathology. MMP-13 and IL-1ß expression was determined by immunohistochemistry and WB. Effects of Rapamycin (10 µM) were analyzed by WB. LC3 and rpS6 expression was determined by WB in chondrocytes from Healthy, Non Diabetic-OA and Diabetic-OA patients.RESULTS:
Insulin downregulates autophagy by reducing LC3 II expression and increasing Akt and rpS6 phosphorylation. Loss of proteoglycans and increased MMP-13 and IL-1ß expression was observed after insulin treatment. Autophagy activation by rapamycin reversed insulin effects. Importantly, chondrocytes from diabetic-OA patients showed decreased LC3 and increased p-rpS6 expression compared to Healthy and Non-Diabetic OA patients.CONCLUSIONS:
These results suggest that decreased autophagy might be a mechanism by which diabetes influences cartilage degradation. Pharmacological activation of autophagy may be an effective therapeutic approach to prevent T2D-induced cartilage damage.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Cartilage, Articular
/
Insulin
Type of study:
Etiology_studies
/
Risk_factors_studies
Limits:
Aged
/
Aged80
/
Humans
/
Middle aged
Language:
En
Journal:
Osteoarthritis Cartilage
Journal subject:
ORTOPEDIA
/
REUMATOLOGIA
Year:
2016
Document type:
Article
Affiliation country: