Abstract: Osteoprotegerin and Receptor Activator of Nuclear Factor-kB Ligand mRNA Expression in Patients with Rheumatoid Arthritis and Healthy Controls

Osteoprotegerin and Receptor Activator of Nuclear Factor-kB Ligand mRNA Expression in Patients with Rheumatoid Arthritis and Healthy Controls

ANN VANDERBORGHT, LOES LINSEN, MARIËLLE THEWISSEN, PIET GEUSENS, JEF RAUS, and PIET STINISSEN

ABSTRACT.

Objective. To further understand the role of osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANK-L) in rheumatoid arthritis (RA), we studied the levels of RANK-L and OPG mRNA in peripheral blood mononuclear cells (PBMC) and synovial tissue of patients with RA and controls.

Methods. RANK-L and OPG mRNA levels were measured in PBMC and CD4+/CD8+ T cell subsets of patients with chronic RA, osteoarthritis (OA), and healthy controls, using quantitative real-time polymerase chain reaction. OPG and RANK-L mRNA levels were measured in paired blood and synovial tissue samples of patients with early, untreated RA at 2 timepoints with an interval of 16 weeks.

Results. RANK-L mRNA levels were significantly higher in PBMC of patients with early and chronic RA compared to healthy controls. Contrary to healthy controls, RANK-L mRNA levels in patients with chronic RA were mainly of CD4+ T cell origin. OPG mRNA was observed in the blood of all (17/17) early RA patients, but could not be detected in chronic RA patients (0/14) or in patients with OA (0/8). Three out of 17 healthy controls showed measurable levels of OPG mRNA. The OPG/RANK-L ratio tended to be higher in the synovium than in the PBMC of early RA patients. RANK-L mRNA in synovial tissue was mainly of non-T cell origin.

Conclusion. Since RANK-L and OPG mRNA levels are elevated in PBMC of RA patients, and CD4+ T cells are the major contributors to RANK-L mRNA expression, mononuclear cells in patients with RA may be involved in the pathways that regulate bone metabolism. (J Rheumatol 2004;31:1483-90)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
OSTEOPROTEGERIN
RECEPTOR ACTIVATOR NUCLEAR FACTOR KAPPA B LIGAND
SYNOVIUM

From Limburgs Universitair Centrum, Biomedisch Onderzoeksinstituut, and Transnationale Universiteit Limburg, School of Life Sciences, Universitaire Campus, Diepenbeek, Belgium.

Supported by grants from "Instituut voor de aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen (IWT)" and "Bijzonder Onderzoeksfonds LUC."

AV and LL contributed equally to this study. A. VanderBorght, PhD; L. Linsen, MSc; M. Thewissen, MSc; P. Geusens, MD, PhD; J. Raus, MD, PhD; P. Stinissen, PhD, Limburgs Universitair Centrum, Biomedisch Onderzoeksinstituut.

Address reprint requests to Dr. P. Stinissen, Biomedisch Onderzoeksinstituut, Limburgs Universitair Centrum, Universitaire Campus, B-3590 Diepenbeek, Belgium. E-mail: piet.stinissen@luc.ac.be.

Submitted August 14, 2003; revision accepted March 24, 2004.