Universität zu Köln

Nam, Jin ORCID: 0000-0001-5117-8958, Perera, Priyangi, Liu, Jie, Rath, Bjoern, Deschner, James, Gassner, Robert, Butterfield, Timothy A. and Agarwal, Sudha (2011). Sequential Alterations in Catabolic and Anabolic Gene Expression Parallel Pathological Changes during Progression of Monoiodoacetate-Induced Arthritis. PLoS One, 6 (9). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Chronic inflammation is one of the major causes of cartilage destruction in osteoarthritis. Here, we systematically analyzed the changes in gene expression associated with the progression of cartilage destruction in monoiodoacetate-induced arthritis (MIA) of the rat knee. Sprague Dawley female rats were given intra-articular injection of monoiodoacetate in the knee. The progression of MIA was monitored macroscopically, microscopically and by micro-computed tomography. Grade 1 damage was observed by day 5 post-monoiodoacetate injection, progressively increasing to Grade 2 by day 9, and to Grade 3-3.5 by day 21. Affymetrix GeneChip was utilized to analyze the transcriptome-wide changes in gene expression, and the expression of salient genes was confirmed by real-time-PCR. Functional networks generated by Ingenuity Pathways Analysis (IPA) from the microarray data correlated the macroscopic/histologic findings with molecular interactions of genes/gene products. Temporal changes in gene expression during the progression of MIA were categorized into five major gene clusters. IPA revealed that Grade 1 damage was associated with upregulation of acute/innate inflammatory responsive genes (Cluster I) and suppression of genes associated with musculoskeletal development and function (Cluster IV). Grade 2 damage was associated with upregulation of chronic inflammatory and immune trafficking genes (Cluster II) and downregulation of genes associated with musculoskeletal disorders (Cluster IV). The Grade 3 to 3.5 cartilage damage was associated with chronic inflammatory and immune adaptation genes (Cluster III). These findings suggest that temporal regulation of discrete gene clusters involving inflammatory mediators, receptors, and proteases may control the progression of cartilage destruction. In this process, IL-1 beta, TNF-alpha, IL-15, IL-12, chemokines, and NF-kappa B act as central nodes of the inflammatory networks, regulating catabolic processes. Simultaneously, upregulation of asporin, and downregulation of TGF-beta complex, SOX-9, IGF and CTGF may be central to suppress matrix synthesis and chondrocytic anabolic activities, collectively contributing to the progression of cartilage destruction in MIA.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nam, Jin UNSPECIFIED orcid.org/0000-0001-5117-8958 UNSPECIFIED Perera, Priyangi UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Jie UNSPECIFIED UNSPECIFIED UNSPECIFIED Rath, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Deschner, James UNSPECIFIED UNSPECIFIED UNSPECIFIED Gassner, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Butterfield, Timothy A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Agarwal, Sudha UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-489088
DOI:	10.1371/journal.pone.0024320
Journal or Publication Title:	PLoS One
Volume:	6
Number:	9
Date:	2011
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ARTICULAR-CARTILAGE; CANDIDATE GENES; RHEUMATIC CONDITIONS; HUMAN OSTEOARTHRITIS; PROFILING REVEALS; PROSTAGLANDIN E-2; BONE; CELL; CHONDROCYTES; MODELS Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48908