DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding
Hyaloid cartilage fibrosis is one of the important reasons for the poor prognosis of advanced osteoarthritis (OA), and is the main factor leading to joint stiffness and deformity. However, the mechanism of hyaline cartilage fibrosis remains largely unclear. Here we report that DDX5, one of the founding members of the DEAD-box RNA helicase family, was dramatically down-regulated in the degenerated articular cartilage of aged mice, and patients with OA, mouse destabilization of the medial meniscus (DMM) models,and cytokine (Interleukin (IL)-1ß and tumor necrosis factor (TNF)-a) stimulation.In vitro and in vivo experimental findings that inhibition of DDX5 expression increases the fibrocartilage phenotype by reduction collagen type I (COL I) protein expression and up-regulate collagen type II (COL II) protein expression. In addition, The reduction of DDX5 aggravate cartilage degradation by induce the production of cartilage degrading enzymes. In addition, DDX5 induced exon 25 skip of FN1-AS and exon 14 skip of PLOD2-AS produced a transcript (termed FN1-AS1-SE25 and PLOD2-AS-SE14). The reduction in DDX5 results in an increase in the FN1-AS-WT and PLOD2-AS-WT variants. Overall design: By comparing the RNA-seq analysis of ATDC5 under the condition of cytokine treatment, explore the alternative splicing in osteoarthritis