Dataset Information

Expression of long non?coding RNAs in chondrocytes from proximal interphalangeal joints.

ABSTRACT: Osteoarthritis (OA) of hand is a common disease, resulting in disability of the hands. The pathogenesis of hand (H) OA remains to be elucidated, and findings from knee and hip joints cannot be simply applied to HOA. To improve knowledge on the specific biology and pathobiology of HOA, the present study performed bioinformatics analyses to analyze the long non?coding (lnc) RNA expression profile in human chondrocytes of proximal interphalangeal (PIP) finger joints and knee joints. Gene expression data were downloaded from the Gene Expression Omnibus database, and PIP and knee chondrocytes were analyzed (n=3/group). Probes of the Affymetrix Human Gene 2.0 ST Microarray were annotated to obtain information about lncRNA expression profile. Compared with chondrocytes from knee joints, chondrocytes derived from PIP joints had significantly different lncRNA expression profiles, and 1,172 lncRNAs were differentially expressed. Compared with chondrocyte from knee joints, 534 lncRNAs were upregulated and 638 lncRNAs were downregulated in chondrocytes from PIP joints. A co?expression network was constructed to analyze the correlation between lncRNAs and protein?coding genes. Function annotation analyses suggested that protein?coding genes that are co?expressed with lncRNAs are enriched in the biological processes of bone morphogenesis, bone development and cartilage development. In conclusion, the present study demonstrated that chondrocytes derived from PIP joints exhibit a significant difference in lncRNA expression compared with chondrocytes derived from knee joints.

SUBMITTER: Lv D

PROVIDER: S-EPMC5647052 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Expression of long non‑coding RNAs in chondrocytes from proximal interphalangeal joints.

Lv Dong D Su Changzheng C Li Zhen Z Chai Xingyu X Xu Zhengwen Z Pang Tao T

Molecular medicine reports 20170817 4

Osteoarthritis (OA) of hand is a common disease, resulting in disability of the hands. The pathogenesis of hand (H) OA remains to be elucidated, and findings from knee and hip joints cannot be simply applied to HOA. To improve knowledge on the specific biology and pathobiology of HOA, the present study performed bioinformatics analyses to analyze the long non‑coding (lnc) RNA expression profile in human chondrocytes of proximal interphalangeal (PIP) finger joints and knee joints. Gene expression ...[more]

PMID: 28849021

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Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA. Three samples of cultured chondrocytes from knee and proximal interphalangeal finger joints were compared. Gene expression of the four most differentially regulated genes was confirmed by real-time PCR in 10 independent samples.

Project description:Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFN?2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFN?2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFN? also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response.

Dataset Information

Expression of long non?coding RNAs in chondrocytes from proximal interphalangeal joints.

Publications

Expression of long non‑coding RNAs in chondrocytes from proximal interphalangeal joints.

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