Synovial tissue in rheumatoid arthritis is a source of osteoclast differentiation factor

Objective. Osteoclast differentiation factor (ODF; also known as osteoprote gerin ligand, receptor activator of nuclear factor kappa B ligand, and tumo r necrosis factor-related activation-induced cytokine) is a recently descri bed cytokine known to be critical in inducing the differentiation of cells of the monocyte/macrophage lineage into osteoclasts. The role of osteoclast s in bone erosion in rheumatoid arthritis (RA) has been demonstrated, but t he exact mechanisms involved in the formation and activation of osteoclasts in RA are not known, These studies address the potential role of ODF and t he bone and marrow microenvironment in the pathogenesis of osteoclast-media ted bone erosion in RA, Methods. Tissue sections from the bone-pannus interface at sites of bone er osion were examined for the presence of osteoclast precursors by the coloca lization of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (T RAP) and cathepsin K in mononuclear cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to identify mRNA for ODF in synovial tiss ues, adherent synovial fibroblasts, and activated T lymphocytes derived fro m patients with RA. Results. Multinucleated cells expressing both TRAP and cathepsin K mRNA wer e identified in bone resorption lacunae in areas of pannus invasion into bo ne in RA patients. In addition, mononuclear cells expressing both TRAP and cathepsin K mRNA (preosteoclasts) were identified in bone marrow in and adj acent to areas of pannus invasion in RA erosions. ODF mRNA was detected by RT-PCR in whole synovial tissues from patients with RA but not in normal sy novial tissues. In addition, ODF mRNA was detected in cultured adherent syn ovial fibroblasts and in activated T lymphocytes derived from RA synovial t issue, which were expanded by exposure to anti-CD3. Conclusion, TRAP-positive, cathepsin K-positive osteoclast precursor cells are identified in areas of pannus invasion into bone in RA. ODF is expresse d by both synovial fibroblasts and by activated T lymphocytes derived from synovial tissues from patients with RA, These synovial cells may contribute directly to the expansion of osteoclast precursors and to the formation an d activation of osteoclasts at sites of bone erosion in RA.