SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Gene.

This study was performed to elucidate the molecular function of the synoviocyte proliferation-associated in collagen-induced arthritis (CIA) 1/serum amyloid A-like 1 (SPACIA1/SAAL1) in mice CIA, an animal model of rheumatoid arthritis (RA), and human RA-synovial fibroblasts (RASFs). -deficient mice were generated and used to create mouse models of CIA in mild or severe disease conditions. Cell cycle-related genes, whose expression levels were affected by small interfering RNA (siRNA), were screened.

Overexpression of SPACIA1/SAAL1, a newly identified gene that is involved in synoviocyte proliferation, accelerates the progression of synovitis in mice and humans.

Objective: To identify novel genes associated with dysregulated proliferation of activated synovial fibroblasts, which are involved in arthritic joint destruction.

Methods: We performed transcriptome analysis to identify genes that were up-regulated in the foot joints of mice with collagen-induced arthritis (CIA). The effect of candidate genes on proliferation of synovial fibroblasts was screened using antisense oligodeoxynucleotides and small interfering RNAs (siRNAs).

Prostaglandin EP2 receptor signalling inhibits the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes.

Objectives: Matrix metalloproteinase (MMP) 13 is a pathogenic collagenase that causes cartilage destruction and plays a leading role in causing osteoarthritis. This study focused on 114 genes that are differentially expressed between intact and damaged osteoarthritis cartilage, in order to determine which molecules are involved in suppressing MMP-13 expression.

Methods: MMP-13 concentrations were measured in the supernatant of human osteoarthritis chondrocyte cultures transfected with small interfering RNA (siRNA) against the 114 genes.

Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage.

Objective: To analyze the differences in gene expression profiles of chondrocytes in intact and damaged regions of cartilage from the same knee joint of patients with osteoarthritis (OA) of the knee.

Methods: We compared messenger RNA expression profiles in regions of intact and damaged cartilage (classified according to the Mankin scale) obtained from patients with knee OA. Five pairs of intact and damaged regions of OA cartilage were evaluated by oligonucleotide array analysis using a double in vitro transcription amplification technique.

New ethacrynic acid derivatives as potent cytoskeletal modulators in trabecular meshwork cells.

A series of ethacrynic acid (ECA) derivatives were synthesized and examined for ocular hypotensive activity. Efficacy was evaluated in a cell-shape assay, using human trabecular meshwork cells, and cytotoxicity in a (3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay, using cultured bovine trabecular meshwork cells. Many of the derivatives demonstrated efficacy equal to or greater than that of ECA.