KLF5 aggravates osteoarthritis progression by inhibiting chondrocyte autophagy via transcriptional activation of PLK2

This study aims to investigate the regulatory role of the Krüppel-like factor 5 (KLF5)/Polo-like kinase 2 (PLK2) axis in osteoarthritis (OA) and its effects on chondrocyte function. An OA mouse model was established. Cartilage damage was assessed by hematoxylin-eosin, Safranin O-Fast Green, and Alcian blue stainings. Serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The expression of PLK2, Bax, Bcl-2, and Cleaved Caspase-3 was evaluated by RT-qPCR and Western blotting. Immunohistochemistry was used to detect the expression of PLK2, Collagen II, MMP13, Beclin-1, and LC3. In OA chondrocytes, following knockdown of PLK2 using sh-PLK2 or KLF5 overexpression, cell viability, apoptosis, extracellular matrix proteins were evaluated. The interaction between KLF5 and the PLK2 promoter was analyzed using ChIP-qPCR and dual-luciferase reporter assays. PLK2 was significantly upregulated in the OA mouse model and was closely associated with cartilage damage and inflammatory responses. Silencing PLK2 or KLF5 promoted chondrocyte autophagy, improved extracellular matrix metabolism, enhanced cell viability, and suppressed apoptosis and inflammatory injury. KLF5 directly bound to the PLK2 promoter to transcriptionally activate its expression, thereby upregulating PLK2, inhibiting autophagy, disrupting cartilage matrix homeostasis, and exacerbating cartilage damage and inflammation in OA mice. KLF5 promotes OA progression by transcriptionally activating PLK2, thereby suppressing chondrocyte autophagy and contributing to cartilage degeneration.