Upregulation of caspase-3 by high glucose in chondrocyte involves the cytoskeleton aggregation.

Abstract

The hyperglycemic environment of diabetes promotes chondrocyte (CH) apoptosis and is closely related to the occurrence and development of osteoarthritis (OA). This present study aimed to elucidate the relation between the cytoskeleton and the caspase-3 expression of human CHs in high glucose in vitro. We used different concentrations of glucose medium to test the effect of glucose on the CHs viability. Cytochalasin D and colchicine were used to prevent the aggregation of F-actin and β-tubulin. Besides, Z-DEVD-FMK (ZDF) or Apoptosis Activator 2 was used to inhibit or activate the caspase-3 expression. The intensity of F-actin and β-tubulin, cell viability, apoptosis, and caspase-3 expression were analyzed. Three days of treatment of 30 mM or 40 mM glucose significantly decreased the CHs viability compared to the 10 mM but increased the caspase-3, apoptosis, collagen, and the aggregation of the F-actin and β-tubulin. However, the cytochalasin D and colchicine partly rejected the high-glucose induced caspase-3 upregulation, apoptosis, and CHs disability. Besides, these two anti-aggregation drugs also suppressed the Apoptosis Activator 2 induced caspase-3 upregulation and apoptosis. Furthermore, the application of ZDF could only prevent the F-actin aggregation, but not the β-tubulin. Long-term high glucose triggers the caspase-3 expression and leads to the CH apoptosis involving cytoskeleton aggregation. Inhibition of cytoskeleton aggregation through the F-actin or β-tubulin could alleviate the high glucose-induced caspase-3 upregulation.