RESEARCH - Anti-TNF therapy increases synovial osteoprotegerin expression in RA

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Arthritis Rheum. 2006 Jan;54(1):76-81.

Anti-tumor necrosis factor therapy increases synovial osteoprotegerin

expression in rheumatoid arthritis.

Catrina AI, Klint EA, Ernestam S, Catrina SB, Makrygiannakis D, Botusan IR,

Klareskog L, Ulfgren AK.

Karolinska University Hospital, Karolinska Institutet, Solna, Sweden, and

Carol Davila University of Medicine, Bucharest, Romania.

OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumor necrosis factor

(TNF)-blocking agents, including etanercept and infliximab, has resulted in

reductions in the radiographic progression of RA. However, the exact

mechanism by which this protection occurs has not been determined. In order

to add to such knowledge, we investigated the effect of anti-TNF therapy on

the expression of osteoprotegerin (OPG) and receptor activator of NF-kappaB

ligand (RANKL) in synovial tissue. METHODS: The expression of OPG and RANKL

in synovial biopsy specimens was evaluated by immunohistochemistry. Serial

synovial biopsy specimens were obtained from 18 patients with RA, before and

after treatment with etanercept (9 patients) or infliximab (9 patients).

Biopsy specimens were evaluated by double-blind semiquantitative analysis

and image analysis. The in vitro effect of TNF antagonists on the RANKL/OPG

expression in osteoblasts and endothelial cells was evaluated by Western

blotting. Statistical analysis was performed using Wilcoxon's signed rank

test, followed by the Bonferroni correction for multiple comparisons of

paired samples. The results of in vitro experiments were evaluated by

one-way analysis of variance, with Tukey's post hoc test. RESULTS: Treatment

with both infliximab and etanercept increased the expression of OPG in

synovial tissue. After 8 weeks of treatment, neither infliximab nor

etanercept influenced RANKL expression. In both groups of patients, the

RANKL:OPG ratio decreased following therapy. In vitro, both of the TNF

antagonists mimicked the in vivo effect, inducing a decrease in the

RANKL:OPG ratio in TNF-primed osteoblasts and endothelial cells. CONCLUSION:

Therapy with TNF antagonists in RA modulates the OPG/RANKL system, a

potential mechanism that could explain the retardation of radiographic

damage observed following anti-TNF therapy.

PMID: 16385498

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6385498 & dopt=Abstract

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