Imbalanced expression of RANKL and osteoprotegerin mRNA in pannus tissue of rheumatoid arthritis

CER3244
2008 Vol.26, N°2
PI 0240, PF 0246
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PMID: 18565244 [PubMed]

Abstract

OBJECTIVES:
To test if the pannus tissue is characterized by a high receptor activator of nuclear factor κB ligand to osteoprotegerin (RANKL:OPG) ratio, which could explain local osteoclastogenesis and formation of bony erosions.
METHODS:
Messenger RNA and protein expressions of RANKL and OPG in rheumatoid and osteoarthritic tissue samples were measured using quantitative real-time RT-PCR and Western blot/densitometry. Pannus and synovitis fibroblasts explanted from tissue samples were cultured in vitro without and with TNF-α, IL-1Β or IL-17 and analyzed quantitatively for RANKL expression. The ability of pannus fibroblasts to induce formation of multinuclear osteoclast-like cells from human monocytes, with macrophage-colony stimulating factor (M-CSF) but without RANKL added, was tested. Histochemical staining was used to assess the eventual presence of RANKL and tartrate resistant acid phosphatase positive osteoclast-like cells at the pannus-bone interface.
RESULTS:
RANKL:OPG ratios of messenger RNA (p<0.05) and protein level were high in pannus (2.06±0.73 and 2.2±0.65) compared to rheumatoid (0.62±0.13 and 1.31±0.69) and osteoarthritis (0.62±0.32 and 0.52±0.16) synovial membranes. Resting and stimulated (p dependent on the cytokine used) pannus fibroblasts produced RANKL in excess (p=0.0005) and unstimulated pannus fibroblasts also effectively induced osteoclast-like cell formation from monocytes in vitro without any exogenous RANKL added. Compatible with these findings, multinuclear osteoclasts-like cells were frequent in the fibroblast- and macrophage-rich pannus tissue at the soft tissue-to-bone interface.
CONCLUSIONS:
The high RANKL:OPG ratio, together with close fibroblast-to-monocyte contacts in pannus tissue, probably favor local generation of bone resorbing osteoclasts at the site of erosion in rheumatoid arthritis.