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.
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Funding
This work was supported by the grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP, Nos. 2015R1C1A2A01055015, 2017R1D1A3B03033401, 2018R1D1A1B07051064, 2020R1I1A306969913, and 2020R1A6A3A01100240).
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Han, Y., Yu, SM., Shah, F.H. et al. Subversive molecular role of Krüppel-like factor 5 in extracellular matrix degradation and chondrocyte dedifferentiation. Funct Integr Genomics 22, 1307–1313 (2022). https://doi.org/10.1007/s10142-022-00892-2
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DOI: https://doi.org/10.1007/s10142-022-00892-2