The Role of PPARγ in Hyperglycemia-induced Deleterious Effect on Chondrocytes

Abstract

Aims: There is a well-established link between OA and diabetes, and study have shown that hyperglycemia might play an important role in the occurrence and development of OA. Accumulative evidence suggested that PPARγ was involved in AGEs-related disease, including diabetes and OA. The study was designed to investigate the effects of hyperglycemia on the expression of PPARγ in chondrocytes and whether PPARγ agonist pioglitazone had a chondroprotective effect.Main methods: Primary human chondrocytes were incubated with different concentration of glucose medium(5.5mM-30mM) in the presence or absence of PPARγ agonist pioglitazone. The AGEs formation level in chondrocytes culture medium was detected by AGEs specific ELISA kits. The expression of IL-1, MMP-13, TNF-α, PPARγ was determined by western blotting and real-time PCR.Key findings: The AGEs fomation level was time-dependently and dose-dependently increased in chondrocyte culture media. Hyperglycemia could enhance the expression of IL-1β, TNF-α, MMP-13, but the level of PPARγ was decreased in a time-dependent and dose-dependent manner, which was inhibited by PPARγ agonist pioglitazone. Noteworthy, the maximum effect was found to at 20mM glucose medium for 24h.Significance: Hyperglycemia could increase the AGEs formation level and induce inflammatory response and matrix degradation reaction in chondrocytes. PPARγ agonists pioglitazone had a chondroprotective effect via inhibit inflammatory response and matrix degradation reaction. PPARγ could be a potential target for pharmacologic intervention in the treatment of diabetic-induced OA.