Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease‐discordant monozygotic twins

Abstract

Objective. To identify disease-specific gene expression profiles in patients with rheumatoid arthritis (RA), using complementary DNA (cDNA) microarray analyses on lymphoblastoid B cell lines (LCLs) derived from RA-discordant monozygotic (MZ) twins.Methods. The cDNA was prepared from LCLs derived from the peripheral blood of 11 pairs of RAdiscordant MZ twins. The RA twin cDNA was labeled with cy5 fluorescent dye, and the cDNA of the healthy co-twin was labeled with cy3. To determine relative expression profiles, cDNA from each twin pair was combined and hybridized on 20,000-element microarray chips. Immunohistochemistry and real-time polymerase chain reaction were used to detect the expression of selected gene products in synovial tissue from patients with RA compared with patients with osteoarthritis and normal healthy controls.Results. In RA twin LCLs compared with healthy co-twin LCLs, 1,163 transcripts were significantly differentially expressed. Of these, 747 were overexpressed and 416 were underexpressed. Gene ontology analysis revealed many genes known to play a role in apoptosis, angiogenesis, proteolysis, and signaling. The 3 most significantly overexpressed genes were laeverin (a novel enzyme with sequence homology to CD13), 11␤-hydroxysteroid dehydrogenase type 2 (a steroid pathway enzyme), and cysteine-rich, angiogenic inducer 61 (a known angiogenic factor). The products of these genes, heretofore uncharacterized in RA, were all abundantly expressed in RA synovial tissues.Conclusion. Microarray cDNA analysis of peripheral blood-derived LCLs from well-controlled patient populations is a useful tool to detect RA-relevant genes and could help in identifying novel therapeutic targets.

C5orf30 is a negative regulator of tissue damage in rheumatoid arthritis

“…This amino acid motif matches the consensus sequence for the basophilic AGC kinases (such as protein kinase B), which regulate cell migration and whose activity is stimulated by integrin binding and interaction with T-cell receptors (21). C5orf30 sequences also contains a motif matching closely the consensus for CDK1 phosphorylation (amino acids [20][21][22][23][24][25][26][27][28][29][30], which coupled to recognition sequences for cyclins (amino acids 139-170) is a strong indication of a roles for C5orf30 in the cell cycle. C5orf30 encodes a basic polypeptide (pI 9.5), a feature typical of proteins interacting with phospholipids, membranes, and/or nucleic acid interactions.…”

Simvastatin inhibits cytokine‐stimulated Cyr61 expression in osteoblastic cells: A therapeutic benefit for arthritis

“…In a rat model of bacteria-induced apical periodontitis, we found that osteoblastic expression of Cyr61 correlates with the severity of inflammation-associated bone loss (12). A complementary DNA microarray analysis of B cells from monozygotic twins revealed significantly higher expression of Cyr61 in twins with RA compared with their healthy cotwins, and that study also showed increased immunoreactivity of Cyr61 in synovial tissue of RA patients (13). Recently, Zhang et al (14) found that Cyr61 plays a critical role in IL-17-mediated proliferation of fibroblast-like synoviocytes in RA.…”

Postoperative Accumulation of Cyr61/CCN1 in Surgical Wound Fluid Precedes Cytokine Activation and is Disparate from Systemic Alterations

“…Studies have connected deregulations of CCN1 to a variety of diseases associated with chronic inflammation, such as rheumatoid arthritis [27], atherosclerosis [28], infectious myocarditis [29], inflammatory bowel disease [30], chronic obstructive pulmonary disorder [31] and several cancers [7]. However, experimental studies have also suggested a role for CCN1 in acute inflammation by demonstrating its ability to promote cytokine secretion [21,32] and support the adhesion of platelets [33], and monocytes/macrophages [21,34].…”