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TGF-? signaling regulates fibrotic expression and activity in carpal tunnel syndrome.

ABSTRACT: Fibrosis of the subsynovial connective tissue (SSCT) is a predominant feature of carpal tunnel syndrome (CTS). While the nature of CTS has been extensively studied, little is known about the etiology of this disease. We investigated SSCT tissue from patients with CTS and control subjects using fibrosis arrays and cell culture analysis. Twofold changes in fibrotic gene expression were found in multiple genes from patient SSCT using fibrosis arrays. This data was confirmed via qRT-PCR on a subset of genes; collagen I (Col1), collagen III (Col3), connective tissue growth factor (CTGF), transforming growth factor ? (TGF-?), and SMAD3 (P?

SUBMITTER: Gingery A

PROVIDER: S-EPMC4222071 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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TGF-β signaling regulates fibrotic expression and activity in carpal tunnel syndrome.

Gingery Anne A Yang Tai-Hua TH Passe Sandra M SM An Kai-Nan KN Zhao Chunfeng C Amadio Peter C PC

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20140730 11

Fibrosis of the subsynovial connective tissue (SSCT) is a predominant feature of carpal tunnel syndrome (CTS). While the nature of CTS has been extensively studied, little is known about the etiology of this disease. We investigated SSCT tissue from patients with CTS and control subjects using fibrosis arrays and cell culture analysis. Twofold changes in fibrotic gene expression were found in multiple genes from patient SSCT using fibrosis arrays. This data was confirmed via qRT-PCR on a subset ...[more]

PMID: 25073432

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Project description:BackgroundFibroblast behavior and cell-matrix interactions of cells from normal and idiopathic carpal tunnel syndrome (CTS) subsynovial connective tissue (SSCT) with and without Triamcinolone Acetonide (TA) were compared in this study. A cell-seeded gel contraction model was applied to investigate the effect of steroid treatment on SSCT fibroblast gene expression and function.MethodsSSCT cells were obtained from CTS patients and fresh cadavers. Cells were isolated by mechanical and collagenase digestion. Collagen gels (1 mg/ml) were prepared with SSCT cells (1 × 106/mL). A sterile Petri dish with a cloning ring in the center was prepared. The area between the ring and outer dish was filled with cell-seeded collagen solution and gelled for 1 h. The gel was released from the outer way of the petri dish to allow gel contraction. Cell seeded gels were treated with 10 M triamcinolone acetonide (TA) or vehicle (DMSO) in modified MEM. Every 4 h for 3 days the contracting gels were photographed and areas calculated. Duplicate contraction tests were performed with each specimen, and the averages were used in the analyses, which were conducted using two-factor analysis of variance in a generalized linear model framework utilizing generalized estimating equations (GEE) to account for the correlation between samples. The contraction rate was determined by the area change over time, and the decay time constant was calculated. A customized mechanical test system was used to determine gel stiffness and tensile strength. Gene expression was assessed using Human Fibrosis and Cell Motility PCR arrays.ResultsTA-treated gels had a significantly higher contraction rate, tensile strength and stiffness than the untreated gels. Proteinases involved in remodeling had increased expression in TA-treated gels of the patient group. Pro-fibrotic genes and ECM regulators, such as TGF-β, collagens and integrins, were down-regulated by TA, indicating that TA may work in part by decreasing fibrotic gene expression.ConclusionsThis study showed that TA affects cell-matrix interaction and suppresses fibrotic gene expression in the SSCT cells of CTS patients.

Dataset Information

TGF-? signaling regulates fibrotic expression and activity in carpal tunnel syndrome.

Publications

TGF-β signaling regulates fibrotic expression and activity in carpal tunnel syndrome.

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