LncRNA WDR11-AS1 Promotes Extracellular Matrix Synthesis in Osteoarthritis by Directly Interacting with RNA-Binding Protein PABPC1 to Stabilize SOX9 Expression

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic bioma...

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Published in:International journal of molecular sciences 2023-01, Vol.24 (1), p.817
Main Authors: Huang, Huang, Yan, Jidong, Lan, Xi, Guo, Yuanxu, Sun, Mengyao, Zhao, Yitong, Zhang, Fujun, Sun, Jian, Lu, Shemin
Format: Article
Language:English
Subjects:
Cartilage, Articular - metabolism
Chondrocytes - metabolism
Extracellular Matrix - metabolism
Humans
Inflammation - metabolism
Membrane Proteins - metabolism
MicroRNAs - genetics
Osteoarthritis - genetics
Osteoarthritis - metabolism
Proto-Oncogene Proteins - metabolism
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
RNA-Binding Proteins - metabolism
SOX9 Transcription Factor - genetics
SOX9 Transcription Factor - metabolism
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Summary:Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as , and the inhibition of PABPC1 improved the mRNA stability of to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA.
ISSN:1422-0067
1422-0067
DOI:10.3390/ijms24010817