Protective effects of atorvastatin against high glucose-induced nuclear factor-κB activation in cultured C28I2 chondrocytes

Abstract

Aims: A number of epidemiological and experimental documents emphasizes a close relation between type 2 diabetes mellitus (T2DM) and the progression of osteoarthritis (OA). In order to understand the underlying mechanisms of atorvastatin (ATO) in OA, we sought to explore the effect of ATO on high glucose (HG)-mediated NF-κB activation in cultured C28I2 chondrocytes.

Methods: The effects of various concentrations of ATO on C28I2 human chondrocytes viability were assessed to obtain the non-cytotoxic concentrations of drug by MTT-assay. The cells were pretreated with 0.01 and 0.1 μM ATO for 6 h, followed by incubation with HG (75 mM) for 72 h. The protein expressions of IκBα (np), IκBα (p), NF-κB (p), and NF-κB (np) were analyzed by western blotting. The effects of ATO on the mRNA expressions of chondrogenic specific markers including SOX9, aggrecan, collagen type 2, and COMP were evaluated by reverse transcription-polymerase chain reaction.

Results: ATO in determined concentrations had no cytotoxic effect on C28I2 cells after 72 h. ATO pretreatment exerted remarkable protective effects against HG-induced cytotoxicity. Moreover, ATO decreased IκBα phosphorylation and NF-κB nuclear translocation. It was also able to improve the gene expression of chondrogenic-specific markers in C28I2 cells compared to the control group.

Conclusion: ATO could significantly decrease HG-induced inflammation in the cultured C28I2 chondrocytes through the activation of canonical NF-κB signaling pathway. These beneficial effects of ATO may be owing to its anti-inflammatory properties. Therefore, treatment with ATO may provide an effective approach to prevent HG-induced cartilage destruction in clinical setting.

Keywords:

• Diabetes mellitus
• high glucose
• osteoarthritis
• inflammation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Iran University of Medical Sciences.