Subversive molecular role of Krüppel-like factor 5 in extracellular matrix degradation and chondrocyte dedifferentiation

Abstract

Osteoarthritis (OA) is the most common joint disorder worldwide and a leading cause of pain and disability. However, the pathogenesis of osteoarthritis has not been elucidated. Krüppel-like factor (KLF)-5 is involved in several biological processes, including inflammation and cell differentiation, but its role in OA has not been evaluated. In this study, we investigated the role of KLF-5 in chondrocyte differentiation. KLF-5 overexpression in chondrocytes induced a loss of type II collagen expression and sulfated proteoglycan synthesis at the transcriptional and translational levels. Based on immunofluorescence staining, the ectopic expression of KLF-5 reduced type II collagen expression. In contrast, with KLF-5-transfected cells, KLF-5 siRNA transfection-induced type II expression also blocked dedifferentiation caused by the overexpression of KLF-5. In zebra fish, KLF-5 reduced the sulfated proteoglycan synthesis of ceratobranchial cartilage. Our results suggest that KLF-5 plays a pivotal role in the dedifferentiation of rabbit articular cartilage and zebra fish, providing a basis for therapeutic strategy for osteoarthritis aimed at controlling cartilage destruction.

Keywords: Articular Cartilages; Chondrocyte; Dedifferentiation; Krüppel-like factor 5; Osteoarthritis.