The Role of Tumor Necrosis Factor-Stimulated Gene 6 Protein (TSG-6) in Osteoarthritis
type: CreativeWork
description: In our studies, we developed a novel method for extracting high quality nucleic acid from joint tissue that relies on finely grinding the desired regions of the knee tibial plateau under liquid nitrogen. By controlling the depth of drill penetration we could reliably separate and isolate articular cartilage and site-matched subchondral bone with high fidelity. We also set up a model system based on specific regions of interest within a joint corresponding to a gradient of disease severities; this system can be used to represent early (relative intact), intermediate (mild to moderate damaged) and late (severe damaged) disease within the knee joints. We performed microarray profiling to identify disease relevant genes and pathways associated with knee OA progression in human articular cartilage. Tumor Necrosis Factor-Stimulated Gene 6 (TSG-6) was identified to be significantly associated with OA progression and validated in both medial and lateral compartment dominant OA samples. Next, we explored mechanisms underlying the association of TSG-6 with OA progression. We characterized the effects of TSG-6, in the presence and absence of inter-alpha-inhibitor (IαI), on anti-plasmin activity, evaluated for the in vivo presence of heavy chains (HCs) in cartilage matrix (evidence of TSG-6 activity), evaluated the gene expression of IαI components and TSG-6 in cartilage, and explored effects of TSG-6 on matrix assembly in vitro. TSG-6 synergized with IαI to inhibit plasmin activity by 39.3%; the presence of HA (full length or fragments) reduced the inhibitory effect. TSG-6 activity was highly correlated (R = 0.6392, P = 0.0006) with TSG-6 protein concentrations in synovial fluid (SF) from knee OA joints. TSG-6 protein and RNA were highly expressed in damaged cartilage from knee tibial and meniscal cartilage and chondrocytes treated with cytokines. The components of the IαI complex, ITIH1, ITIH2, and AMBP genes were either not expressed or expressed at a low level in intact or …
abstract: In our studies, we developed a novel method for extracting high quality nucleic acid from joint tissue that relies on finely grinding the desired regions of the knee tibial plateau under liquid nitrogen. By controlling the depth of drill penetration we could reliably separate and isolate articular cartilage and site-matched subchondral bone with high fidelity. We also set up a model system based on specific regions of interest within a joint corresponding to a gradient of disease severities; this system can be used to represent early (relative intact), intermediate (mild to moderate damaged) and late (severe damaged) disease within the knee joints. We performed microarray profiling to identify disease relevant genes and pathways associated with knee OA progression in human articular cartilage. Tumor Necrosis Factor-Stimulated Gene 6 (TSG-6) was identified to be significantly associated with OA progression and validated in both medial and lateral compartment dominant OA samples. Next, we explored mechanisms underlying the association of TSG-6 with OA progression. We characterized the effects of TSG-6, in the presence and absence of inter-alpha-inhibitor (IαI), on anti-plasmin activity, evaluated for the in vivo presence of heavy chains (HCs) in cartilage matrix (evidence of TSG-6 activity), evaluated the gene expression of IαI components and TSG-6 in cartilage, and explored effects of TSG-6 on matrix assembly in vitro. TSG-6 synergized with IαI to inhibit plasmin activity by 39.3%; the presence of HA (full length or fragments) reduced the inhibitory effect. TSG-6 activity was highly correlated (R = 0.6392, P = 0.0006) with TSG-6 protein concentrations in synovial fluid (SF) from knee OA joints. TSG-6 protein and RNA were highly expressed in damaged cartilage from knee tibial and meniscal cartilage and chondrocytes treated with cytokines. The components of the IαI complex, ITIH1, ITIH2, and AMBP genes were either not expressed or expressed at a low level in intact or …
author: Chou, Chingheng
keywords: Medicine, Articular cartilage, Gene expression profiling, Inter-alpha-inhibitor, Osteoarthritis, Subchondral bone, TSG-6
date published: 2017
date modified: 2026-07-24T02:07:05Z
provider: Duke University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Duke University

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10161/14502