被撤回的出版物: Long noncoding RNA LINC00671 exacerbates osteoarthritis by promoting ONECUT2-mediated Smurf2 expression and extracellular matrix degradation (Retracted article. See vol. 117, 2023)

Accumulating evidence has highlighted the remarkable role of long noncoding RNAs (lncRNAs) in the pathogenesis of various diseases including osteoarthritis (OA). Since current treatment available for OA has limited efficacy, it is urgent to elucidate the pathogenesis of OA. Therefore, we aimed at elucidating the specific regulatory role of LINC00671 in OA progression. Differentially expressed lncRNAs were initially screened using the OA profile. LINC00671, ONECUT2, and Smurf2 expression in OA cartilage tissues were determined, while their interaction was verified by RNA-pull down assay, ChIP, and dual-luciferase reporter gene assay. After chondrocytes were transfected with shRNA and overexpressed plasmids, the proliferation and apoptosis were determined. Meanwhile, extracellular matrix (ECM)-related proteins were detected by Western blot analysis. Establishment of the OA model was performed by surgical destabilization of the medial meniscus (DMM) surgery in mice. Upregulation of LINC00671, ONECUT2, and Smurf2 expression were detected in OA cartilage. LINC00671 was bound to ONECUT2 and ONECUT2 was conjugated to Smurf2. Overexpression of LINC00671 resulted in inhibited chondrocytes proliferation, enhanced apoptosis, and ECM degradation, which was readily reversed by silencing ONECUT2 or Smurf2. Furthermore, LINC00671 induced GSK-3 beta ubiquitination and upregulated beta-catenin expression through Smurf2. In vivo experiment revealed that silencing of LINC00671 or GSK-3 beta activator resulted in alleviated ECM degradation and ameliorated OA progression. Collectively, these data demonstrated that LINC00671 exacerbates OA progression through GSK-3 beta ubiquitination by upregulating ONECUT2-mediated Smurf2.

Automated summary

Accumulating evidence has highlighted the significant role of long noncoding RNAs (lncRNAs) in diseases like osteoarthritis (OA). This study aimed to elucidate the specific regulatory role of LINC00671 in OA progression through interactions with ONECUT2 and Smurf2. The findings suggest that overexpression of LINC00671 exacerbates OA by promoting GSK-3 beta ubiquitination via ONECUT2-mediated Smurf2, leading to inhibited chondrocyte proliferation, enhanced apoptosis, and ECM degradation. Silencing LINC00671 or activating GSK-3 beta showed promise in alleviating ECM degradation and ameliorating OA progression in vivo.