Glucosamine promotes chondrocyte proliferation via the Wnt/ß­catenin signaling pathway.

ABSTRACT

The present study investigated the mechanism underlying the effects of glucosamine (GlcN) on the proliferation of chondrocytes isolated from the knee cartilage of Sprague­Dawley rats. Chondrocytes were treated with various concentrations of GlcN or without GlcN. The effects of GlcN on chondrocyte proliferation were determined using reverse transcription­polymerase chain reaction, western blot analysis and immunohistochemistry. The results indicated that GlcN significantly improved chondrocyte viability, accelerated G1/S transition during progression of the cell cycle and promoted the expression of cell cycle regulatory proteins, including cyclin D1, cyclin­dependent kinase (CDK)4 and CDK6, thus indicating that GlcN may promote chondrocyte proliferation. Furthermore, GlcN upregulated the expression levels of Wnt­4, Frizzled­2 and ß­catenin, and downregulated the expression of glycogen synthase kinase­3. GlcN also promoted ß­catenin translocation; ß­catenin is able to activate numerous downstream target genes, including cyclin D1. To determine the role of the Wnt/ß­catenin signaling pathway in chondrocyte proliferation, the Wnt/ß­catenin signaling pathway was inhibited using Dickkopf­1 (DKK­1), after which chondrocytes were treated with GlcN. The results demonstrated that the expression levels of ß­catenin and cyclin D1 were decreased in chondrocytes treated with DKK­1 and GlcN. These results suggested that GlcN may promote chondrocyte proliferation via the Wnt/ß­catenin signaling pathway.