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Telomerase transduced osteoarthritis fibroblast-like synoviocytes display a distinct gene expression profile.

ABSTRACT: To examine the differential gene expression in telomerase transduced osteoarthritis fibroblast-like synoviocytes (hTERT-OA 13A FLS) and telomerase transduced rheumatoid arthritis FLS (hTERT-RA 516 FLS) and test the hypothesis that longterm culture of hTERT-OA 13A FLS display a disease-specific gene expression profile.Gene expression in passage 8 hTERT-OA 13A FLS and passage 8 hTERT-RA 516 FLS were compared using microarray assays. Differential expression of selected genes was further examined by reverse transcription-polymerase chain reaction (RT-PCR). After continuous expansion in culture for an additional 4 months, gene expression in the longterm cultures of hTERT-OA 13A FLS and hTERT-RA 516 FLS was again examined with microarray and real-time RT-PCR.hTERT-OA 13A FLS displayed a distinct gene expression profile. While hTERT-RA 516 FLS expressedADAMTS1, ADAMTS3, ADAMTS5, and several carboxypeptidases, hTERT-OA 13A FLS expressed matrix metalloproteinase (MMP)1, MMP3, and several cathepsins at higher levels. Numerous genes classified in the immune response, lipid transport/catabolism, and phosphate transport biological processes were also expressed at higher levels in hTERT-OA 13A FLS. In contrast, numerous genes classified in the positive regulation of cell proliferation, anti-apoptosis, and angiogenesis biological processes were expressed at higher levels in hTERT-RA 516 FLS. Further, of the recently proposed 21 candidate synovial biomarkers of OA, 12 (57%) were detected in our study.The findings indicate that OA FLS may not be a passive bystander in OA and that telomerase transduced OA FLS offer an alternative tool for the study of synovial disease markers and for the identification of new therapeutic targets for OA therapy.

SUBMITTER: Sun Y

PROVIDER: S-EPMC2689317 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Telomerase transduced osteoarthritis fibroblast-like synoviocytes display a distinct gene expression profile.

Sun Yubo Y Mauerhan David R DR Firestein Gary S GS Loeffler Bryan J BJ Hanley Edward N EN Gruber Helen E HE

The Journal of rheumatology 20090101 1

<h4>Objective</h4>To examine the differential gene expression in telomerase transduced osteoarthritis fibroblast-like synoviocytes (hTERT-OA 13A FLS) and telomerase transduced rheumatoid arthritis FLS (hTERT-RA 516 FLS) and test the hypothesis that longterm culture of hTERT-OA 13A FLS display a disease-specific gene expression profile.<h4>Methods</h4>Gene expression in passage 8 hTERT-OA 13A FLS and passage 8 hTERT-RA 516 FLS were compared using microarray assays. Differential expression of sele ...[more]

PMID: 19040300

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Project description:High mobility group box 1 (HMGB1) is an important downstream product of pyroptosis in macrophages, and it serves a vital role in numerous inflammatory diseases. Previous studies have reported that HMGB1 is released by fibroblast‑like synoviocytes (FLSs) that are activated by inflammatory cytokines in knee osteoarthritis (KOA); however, the mechanism via which FLS promotes HMGB1 secretion in KOA remains unknown. According to our previous study, pyroptosis occurs in FLSs of patients with KOA and is mediated by Nod‑like receptor protein (NLRP)1 or NLRP3 inflammasomes. However, the specific relationship between HMGB1 secretion and FLS pyroptosis requires further investigation. In the present study, the association between HMGB1 secretion and FLS pyroptosis was investigated in vitro and in vivo. In this study, western blotting, ELISA and reverse transcription‑quantitative PCR were used to measure expression levels of proteins and mRNA. Caspase‑1 activity assay and Hoechst 33342/PI double staining were used to observe the pyroptosis of FLSs. Hematoxylin and eosin staining was used to observe the destruction of cartilage in KOA. Increased expression levels of pyroptosis‑related proteins and HMGB1 in the synovium of rat anterior cruciate ligament transection‑induced KOA models were identified, and these changes were significantly mitigated via the intra‑articular injection of a caspase‑1 inhibitor. In vitro, FLSs were treated with lipopolysaccharide (LPS) + ATP to induce pyroptosis, and HMGB1 secretion was subsequently measured. LPS + ATP significantly increased the expression levels of pyroptosis‑related proteins and HMGB1 in FLSs, and these effects were significantly mitigated by small interfering RNAs targeting NLRP1, NLRP3, apoptosis‑associated speck‑like protein with a caspase‑recruitment domain or caspase‑1. Therefore, the present results indicated that NLRP1/NLRP3 inflammasome‑mediated and caspase‑1‑dependent FLS pyroptosis increased HMGB1 secretion in KOA. These findings may provide a therapeutic strategy to decrease synovial inflammatory responses during KOA progression.

Dataset Information

Telomerase transduced osteoarthritis fibroblast-like synoviocytes display a distinct gene expression profile.

Publications

Telomerase transduced osteoarthritis fibroblast-like synoviocytes display a distinct gene expression profile.

Similar Datasets

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