LncRNA CRNDE hinders the progression of osteoarthritis by epigenetic regulation of DACT1.

Osteoarthritis (OA) is mainly characterized by articular cartilage degeneration, synovial fibrosis, and inflammation. LncRNA CRNDE (colorectal neoplasia differentially expressed) has been reported to be down-regulated in age-related OA, but its role in injury-induced OA needs to be further explored. In this study, an OA rat model was established using anterior cruciate ligament transection, and the adenovirus-mediated CRNDE overexpression (Ad-CRNDE) or DACT1 (dapper antagonist of catenin-1) interference (sh-DACT1) vectors were administered by intraarticular injection. Moreover, chondrocyte‑like ATDC5 cells were treated with IL-1β (10 ng/mL) to simulate OA conditions in vitro. We found that overexpression of CRNDE alleviated cartilage damage and synovitis in OA rats, and suppressed IL-1β-induced apoptosis, inflammation, and extracellular matrix (ECM) degradation in chondrocyte‑like ATDC5 cells, while silencing DACT1 effectively antagonized the protective effect of CRNDE both in vivo and in vitro. Mechanism studies revealed that DACT1 could act as a downstream target of CRNDE. By recruiting p300, CRNDE promoted the enrichment of H3K27ac in the DACT1 promoter, thus promoting DACT1 transcription. In addition, CRNDE hindered the activation of the Wnt/β-catenin pathway in IL-1β-stimulated cells by inducing DACT1 expression. In conclusion, CRNDE promoted DACT1 expression through epigenetic modification and restrained the activation of Wnt/β-catenin signaling to impede the progression of OA.