Transcriptome analysis reveals specific changes in osteoarthritis synovial fibroblasts.
OBJECTIVE
Changes in rheumatoid arthritis synovial fibroblast (RASF) gene expression are usually defined by a comparison to osteoarthritis synovial fibroblasts (OASFs). This study was undertaken to analyse the transcriptome of OASFs as compared to RASFs and healthy synovial fibroblasts (HSFs).


METHODS
The authors used microarray messenger RNA expression profiling of synovial fibroblasts cultured from osteoarthritis (OA), rheumatoid arthritis and normal synovial tissues. Quantitative real-time PCR of selected genes was performed to validate microarray data. Analysis of variance, Student t test and the Benjamini-Hochberg multiple testing correction method for multiple testing correction were used to determine the statistical significance of the changes between the three groups.


RESULTS
Larger numbers of transcripts showed a differential expression in OASFs versus the other groups, rather than in RASFs versus HSFs. Cluster analysis confirmed that the differences between the three groups were mostly due to the differences between OA and the other groups. Functional classification identified a significant number of genes related to growth factor activities, cell adhesion, neurotransmission and Ras signalling that are differentially expressed in OASFs. Classical proinflammatory factors or proteases involved in cartilage degradation were not found to be overexpressed in OASFs.


CONCLUSIONS
Cultured OASFs display a more homogeneous transcriptomic profile than RASFs when compared to HSFs. This supports the participation of synovial fibroblasts in the pathogenesis of OA and may reflect global defects in the mesenchyma-derived lineages of the different tissues in OA joints. These data support individual heterogeneity among RASFs and advise against the use of OASFs as controls.
Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
Manuel J
MJ
Del Rey
Alicia
A
Usategui
Elena
E
Izquierdo
Juan D
JD
Cañete
Francisco J
FJ
Blanco
Gabriel
G
Criado
José L
JL
Pablos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics; D016000:Cluster Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D006133:Growth Substances