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Telomerase Transduced Osteoarthritis Fibroblast-Like Synoviocytes Display a Distinct Gene Expression Profile YUBO SUN, DAVID R. MAUERHAN, GARY S. FIRESTEIN, BRYAN J. LOEFFLER, EDWARD N. HANLEY, and HELEN E. GRUBER
ABSTRACT. 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 expressed ADAMTS1, 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. Conclusion. 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. (J Rheumatol First Release Dec 1 2008; doi:10.3899/jrheum.080505 Key Indexing Terms:
OSTEOARTHRITIS
From the Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina; and the Division of Rheumatology, Allergy and Immunology, University of California San Diego, School of Medicine, La Jolla, California, USA. Supported in part by a Charlotte-Mecklenburg Science Services Foundation grant to Y.S., and NIH Grant R01 AR45347 to G.S.F. Y. Sun, PhD, Senior Scientist; D.R. Mauerhan, MD, Orthopaedic Surgeon; B.J. Loeffler, MD, Orthopaedic Resident; E.N. Hanley, MD, Orthopaedic Surgeon and Chairman; H.E. Gruber, PhD, Senior Scientist and Director of Orthopaedic Research Biology, Department of Orthopaedic Surgery, Carolinas Medical Center; G.S. Firestein, Professor and Chief, Division of Rheumatology, Allergy and Immunology, University of California San Diego, School of Medicine. Address reprint requests to Dr. Y. Sun, Department of Orthopaedic Surgery, Biology Division, Cannon Research 304, Carolinas Medical Center, Charlotte, NC 28232, USA. E-mail: yubo.sun@carolinashealthcare.org Accepted for publication August 6, 2008.
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