Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

Li, Chenshuang; Zheng, Zhong

doi:10.3390/ijms21176033

Cited by 10 publications

(15 citation statements)

References 81 publications

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“…Synovitis is common in OA and may augment cartilage damage, which has been a therapeutic target of OA ( Labinsky et al, 2020 ). Synovitis is characterized by synovial tissue hyperplasia, inner macrophage aggregation as well as cell secretion disfunction ( Li and Zheng, 2020 ). The immune system that is involved in the initiation and progression of OA is a key element in the pathogenesis of this disease ( Zhang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression

Liu

Chen

Zeng

et al. 2022

Front. Mol. Biosci.

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Objective: Osteoarthritis (OA) is the most common chronic degenerative joint disease, which represents the leading cause of age-related disability. Here, this study aimed to depict the intercellular heterogeneity of OA synovial tissues.Methods: Single-cell RNA sequencing (scRNA-seq) data were preprocessed and quality controlled by the Seurat package. Cell cluster was presented and cell types were annotated based on the mRNA expression of corresponding marker genes by the SingleR package. Cell-cell communication was assessed among different cell types. After integrating the GSE55235 and GSE55457 datasets, differentially expressed genes were identified between OA and normal synovial tissues. Then, differentially expressed marker genes were overlapped and their biological functions were analyzed.Results: Totally, five immune cell subpopulations were annotated in OA synovial tissues including macrophages, dendritic cells, T cells, monocytes and B cells. Pseudo-time analysis revealed the underlying evolution process in the inflammatory microenvironment of OA synovial tissue. There was close crosstalk between five cell types according to the ligand-receptor network. The genetic heterogeneity was investigated between OA and normal synovial tissues. Furthermore, functional annotation analysis showed the intercellular heterogeneity across immune cells in OA synovial tissues.Conclusion: This study offered insights into the heterogeneity of OA, which provided in-depth understanding of the transcriptomic diversities within synovial tissue. This transcriptional heterogeneity may improve our understanding on OA pathogenesis and provide potential molecular therapeutic targets for OA.

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Section: Introductionmentioning

confidence: 99%

Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression

Liu

Chen

Zeng

et al. 2022

Front. Mol. Biosci.

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“…The articles were either defined as a retrospective or prospective. The two retrospective studies obtained their RNAseq data from the NCBI GEO DataSets ( https://www.ncbi.nlm.nih.gov/gds ), in which one used the data from United States Human OA subjects ( Li and Zheng 2020 ) and the other used Australian Human OA subjects ( Tsai et al, 2020 ). In the three prospective studies, one used a post-traumatic equine model, and two used synovial tissue obtained prior to arthroplasty of either the hip or knee in human subjects ( Steinberg et al, 2021 ; Huang et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

“…Li et al also found there are 7 genes that were significantly altered that contribute to the functionality of the Extracellular Matrix (ECM). Those 7 genes are Myocilin (MYOC), Amelotin (AMTN), Chitinase-3-like protein 2 (CHI3L2), Prolyl endopeptidase Fibroblast activation protein alpha (FAP), Leucine-rich repat-containing protein 15 (LRRC15), Matrix Metallopeptidase-13 (MMP13), TNFAIP6 (C. Li and Zheng 2020 ).…”

Section: Resultsmentioning

confidence: 99%

RNAseq of Osteoarthritic Synovial Tissues: Systematic Literary Review

2022

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Osteoarthritis (OA) is one of the most common causes of disability in aged people, and it is defined as a degenerative arthropathy, characterized by the disruption in joint tissue. The synovium plays a vital role in maintaining the health of the joint by supplying the nutrients to the surrounding tissues and the lubrication for joint movement. While it is well known that all the joint tissues are communicating and working together to provide a functioning joint, most studies on OA have been focused on bone and cartilage but much less about synovium have been reported. The purpose of this review was to investigate the current literature focused on RNA sequencing (RNAseq) of osteoarthritic synovial tissues to further understand the dynamic transcriptome changes occurring in this pivotal joint tissue. A total of 3 electronic databases (PubMed, CINHAL Complete, and Academic Complete) were systematically searched following PRISMA guidelines. The following criteria was used for inclusion: English language, free full text, between the period 2011–2022, size of sample (n > 10), study design being either retrospective or prospective, and RNAseq data of synovial tissue from OA subjects. From the initial search, 174 articles, 5 met all of our criteria and were selected for this review. The RNAseq analysis revealed several differentially expressed genes (DEGs) in synovial tissue. These genes are related to the inflammatory pathway and regulation of the extracellular matrix. The MMP family, particularly MMP13 was identified by three of the studies, indicating its important role in OA. IL6, a key contributor in the inflammation pathway, was also identified in 3 studies. There was a total of 8 DEGs, MMP13, MMP1, MMP2, APOD, IL6, TNFAIP6, FCER1G, and IGF1 that overlapped in 4 out of the 5 studies. One study focused on microbial RNA in the synovial tissue found that the microbes were differentially expressed in OA subjects too. These differentially expressed microbes have also been linked to the inflammatory pathway. Further investigation with more clinical gene profiling in synovial tissue of OA subjects is required to reveal the causation and progression, as well as aid in the development of new treatments.

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“…Among the 21 differentially expressed lncRNAs, we identified LINC01411 (FC = 6.19, FDR = 2.20 × 10 −8 ) as the most significantly and highest upregulated lncRNA, AC005165.1 (FC = 0.44, FDR = 2.37 × 10 −6 ) as the most significantly downregulated lncRNA and EMX2OS as the most downregulated lncRNA (FC = 0.41, FDR = 7.64 × 10 −3 ). The function of LINC0411 remains unknown, however in a recent study it was found to be differentially expressed between healthy and OA articular cartilage and between healthy and OA synovium, indicating its role in OA across multiple tissues [ 19 ]. According to biotype classification of Ensembl v97 [ 18 ], AC005165.1 was classified as a novel transcript and its function is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA expression profiling of subchondral bone reveals AC005165.1 modifying FRZB expression during osteoarthritis

et al. 2021

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Objective To gain insight in the expression profile of long non-coding RNAs (lncRNAs) in OA subchondral bone. Methods 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, Research osteoArthrits Articular Tissue (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 locked nucleic acid (LNA) GapmeRs targeting AC005165.1 lncRNA, to functionally investigate its potential mRNA targets. Results 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 [false discovery rate (FDR) < 0.05, fold change (FC) range 1.19–7.39], including long intergenic non-protein coding RNA (LINC) 1411 (LINC01411, FC = 7.39, FDR = 2.20 × 10−8), AC005165.1 (FC = 0.44, FDR = 2.37 × 10−6) and empty spiracles homeobox 2 opposite strand RNA (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 frizzled related protein (FRZB). Conclusion 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.

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Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

Cited by 10 publications

References 81 publications

Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression

Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression

RNAseq of Osteoarthritic Synovial Tissues: Systematic Literary Review

Long non-coding RNA expression profiling of subchondral bone reveals AC005165.1 modifying FRZB expression during osteoarthritis

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