Telomerase transduced osteoarthritis fibroblast-like synoviocytes display a distinct gene expression profile.
OBJECTIVE
To examine the differential gene expression in telomerase transduced osteoarthritis fibroblast-like synoviocytes (hTERT-OA 13A FLS) and telomerase transduced rheumatoid arthritis FLS (hTERT-RA 516 FLS) and test the hypothesis that longterm culture of hTERT-OA 13A FLS display a disease-specific gene expression profile.


METHODS
Gene expression in passage 8 hTERT-OA 13A FLS and passage 8 hTERT-RA 516 FLS were compared using microarray assays. Differential expression of selected genes was further examined by reverse transcription-polymerase chain reaction (RT-PCR). After continuous expansion in culture for an additional 4 months, gene expression in the longterm cultures of hTERT-OA 13A FLS and hTERT-RA 516 FLS was again examined with microarray and real-time RT-PCR.


RESULTS
hTERT-OA 13A FLS displayed a distinct gene expression profile. While hTERT-RA 516 FLS expressedADAMTS1, ADAMTS3, ADAMTS5, and several carboxypeptidases, hTERT-OA 13A FLS expressed matrix metalloproteinase (MMP)1, MMP3, and several cathepsins at higher levels. Numerous genes classified in the immune response, lipid transport/catabolism, and phosphate transport biological processes were also expressed at higher levels in hTERT-OA 13A FLS. In contrast, numerous genes classified in the positive regulation of cell proliferation, anti-apoptosis, and angiogenesis biological processes were expressed at higher levels in hTERT-RA 516 FLS. Further, of the recently proposed 21 candidate synovial biomarkers of OA, 12 (57%) were detected in our study.


CONCLUSIONS
The findings indicate that OA FLS may not be a passive bystander in OA and that telomerase transduced OA FLS offer an alternative tool for the study of synovial disease markers and for the identification of new therapeutic targets for OA therapy.
Sun
Yubo
Y
Department of Orthopaedic Surgery, Biology Division, Cannon Research 304, Carolinas Medical Center, Charlotte, NC 28232, USA. yubo.sun@carolinashealthcare.org
Mauerhan
David R
DR
Firestein
Gary S
GS
Loeffler
Bryan J
BJ
Hanley
Edward N
EN
Gruber
Helen E
HE
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology / Q000502:physiology*; D019098:Telomerase / Q000235:genetics; D014161:Transduction, Genetic
D005819:Genetic Markers; D019098:Telomerase