Rheumatology Advance Access published online on February 20, 2006
Rheumatology, doi:10.1093/rheumatology/kel045
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1 Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
* To whom correspondence should be addressed. Objectives. Receptor activator of NF- Methods. Tissues from 20 surgical procedures from 17 patients with RA were collected as discarded materials. Six samples contained only synovium or tenosynovium remote from bone, four samples contained pannus-bone interface with adjacent synovium and 10 samples contained both synovium remote from bone and pannus-bone interface with adjacent synovium. Immunohistochemistry was used to characterize the cellular pattern of RANKL, RANK and OPG protein expression immediately adjacent to and remote from sites of bone erosion. Results. Cellular expression of RANKL protein was relatively restricted in the bone microenvironment; staining was focal and confined largely to sites of osteoclast-mediated erosion at the pannus-bone interface and at sites of subchondral bone erosion. RANK-expressing osteoclast precursor cells were also present in these sites. OPG protein expression was observed in numerous cells in synovium remote from bone but was more limited at sites of bone erosion, especially in regions associated with RANKL expression. Conclusions. The pattern of RANKL and OPG expression and the presence of RANK-expressing osteoclast precursor cells at sites of bone erosion in RA contributes to the generation of a local microenvironment that favours osteoclast differentiation and activity. These data provide further evidence implicating RANKL in the pathogenesis of arthritis-induced joint destruction.
Received October 12, 2005
Accepted January 13, 2006
Original Article
RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion in rheumatoid arthritis
A. R. Pettit 1,
N. C. Walsh 2,
C. Manning 2,
S. R. Goldring 2,
and
E. M. Gravallese 2 *
2 Beth Israel Deaconess Medical Center, New England Baptist Bone and Joint Institute, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, MA 02115, USA
E. M. Gravallese, E-mail: egravall{at}bidmc.harvard.edu
Abstract 
B ligand (RANKL) and osteoprotegerin (OPG) have been demonstrated to be critical regulators of osteoclast generation and activity. In addition, RANKL has been implicated as an important mediator of bone erosion in rheumatoid arthritis (RA). However, the expression of RANKL and OPG at sites of pannus invasion into bone has not been examined. The present study was undertaken to further elucidate the contribution of this cytokine system to osteoclastogenesis and subsequent bone erosion in RA by examining the pattern of protein expression for RANKL, OPG and the receptor activator of NF-B (RANK) in RA at sites of articular bone erosion.
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