00 LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 5 (LRP5) GENE EXPRESSION IN HUMAN OSTEOARTHRITIC CHONDROCYTES

Abstract

The Wnt/b-catenin signaling pathway participates in normal adult bone and cartilage biology and seems to be involved in cartilage degeneration and subsequent OA progression. The aim of this study was to investigate the activation of Wnt/b-catenin pathway in osteoarthritis and the role of LRP5, a coreceptor of Wnt/b-catenin pathway, in human osteoarhritic chondrocytes.

Human cartilage was obtained from 11 patients with primary osteoarthritis (OA) undergoing total knee and hip replacement surgery. Normal cartilage was obtained from 5 healthy individuals. b-catenin and LRP5 mRNA and protein levels were investigated using real time PCR and western blot analysis, respectively. Blocking LRP5 expression was performed using small interfering (siRNA) against LRP5 and subsequent MMP-13 mRNA and protein levels were evaluated by real time RCR and western blot analysis, respectively.

We confirmed the activation of Wnt/b-catenin pathway in osteoarthritis, as we observed significant upregulation of b-catenin mRNA and protein expression in osteoarthritic chondrocytes. We also observed that LRP5 mRNA and protein expression was significantly up-regulated in osteoarthritic cartilage compared to normal. Also, blocking LRP5 expression using siRNA against LRP5 resulted in a significant decrease in MMP-13 mRNA and protein expressions.

Our findings suggest that the upregulation of LRP5 mRNA and protein expression in osteoarthritic chondrocytes results in an increased activation of Wnt/b-catenin pathway in osteoarthritis. The observed reduction of MMP-13 expression after blocking LRP5 expression in osteoarthritic chondrocytes, suggests the involvement of LRP5 in the progression and pathogenesis of osteoarthritis.