Long non-coding RNA expression profiling of subchondral bone reveals AC005165.1 modifying FRZB expression during osteoarthritis | November 3 2021 | Rheumatology – https://doi.org/10.1093/rheumatology/keab826
Abstract
To gain insight in the expression profile of long non-coding RNAs in osteoarthritis (OA) subchondral bone.
RNA sequencing data of macroscopically preserved and lesioned OA subchondral bone of patients that underwent joint replacement surgery due to OA (N = 22 pairs; 5 hips, 17 knees, RAAK-study) was run through an in-house pipeline to detect expression of lncRNAs. Differential expression analysis between preserved and lesioned bone was performed. Spearman correlations were calculated between differentially expressed lncRNAs and differentially expressed mRNAs identified previously in the same samples. Primary osteogenic cells were transfected with LNA GapmeRs targeting AC005165.1 lncRNA, to functionally investigate its potential mRNA targets.
In total 2816 lncRNAs were well-expressed in subchondral bone and we identified 233 lncRNAs exclusively expressed in knee and 307 lncRNAs exclusively in hip. Differential expression analysis, using all samples (N = 22 pairs; 5 hips, 17 knees), resulted in 21 differentially expressed lncRNAs (FDR < 0.05, FC range : 1.19–7.39), including LINC01411 (FC = 7.39, FDR = 2.20×10−8), AC005165.1 (FC = 0.44, FDR = 2.37×10−6), and EMX2OS (FC = 0.41, FDR = 7.64×10−3). Among the differentially expressed lncRNAs, five were also differentially expressed in articular cartilage, including AC005165.1, showing similar direction of effect. Downregulation of AC005165.1 in primary osteogenic cells resulted in consistent downregulation of highly correlated FRZB.
Abstract
To gain insight in the expression profile of long non-coding RNAs in osteoarthritis (OA) subchondral bone.
RNA sequencing data of macroscopically preserved and lesioned OA subchondral bone of patients that underwent joint replacement surgery due to OA (N = 22 pairs; 5 hips, 17 knees, RAAK-study) was run through an in-house pipeline to detect expression of lncRNAs. Differential expression analysis between preserved and lesioned bone was performed. Spearman correlations were calculated between differentially expressed lncRNAs and differentially expressed mRNAs identified previously in the same samples. Primary osteogenic cells were transfected with LNA GapmeRs targeting AC005165.1 lncRNA, to functionally investigate its potential mRNA targets.
In total 2816 lncRNAs were well-expressed in subchondral bone and we identified 233 lncRNAs exclusively expressed in knee and 307 lncRNAs exclusively in hip. Differential expression analysis, using all samples (N = 22 pairs; 5 hips, 17 knees), resulted in 21 differentially expressed lncRNAs (FDR < 0.05, FC range : 1.19–7.39), including LINC01411 (FC = 7.39, FDR = 2.20×10−8), AC005165.1 (FC = 0.44, FDR = 2.37×10−6), and EMX2OS (FC = 0.41, FDR = 7.64×10−3). Among the differentially expressed lncRNAs, five were also differentially expressed in articular cartilage, including AC005165.1, showing similar direction of effect. Downregulation of AC005165.1 in primary osteogenic cells resulted in consistent downregulation of highly correlated FRZB.
The current study identified a novel lncRNA, AC005165.1, being dysregulated in OA articular cartilage and subchondral bone. Downregulation of AC005165.1 caused a decreased expression of OA risk gene FRZB, an important member of the wnt-pathway, suggesting that AC005165.1 could be an attractive potential therapeutic target with effects in articular cartilage and subchondral bone.
The current study identified a novel lncRNA, AC005165.1, being dysregulated in OA articular cartilage and subchondral bone. Downregulation of AC005165.1 caused a decreased expression of OA risk gene FRZB, an important member of the wnt-pathway, suggesting that AC005165.1 could be an attractive potential therapeutic target with effects in articular cartilage and subchondral bone.