The role of interleukin 11 in bone resorption by rheumatoid synovial cells

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Inflammatory bone resorption is an important factor for joint destruction of rheumatoid arthritis (RA). Since osteoclasts play important roles in the bone resorption, we examined about the mechanism of osteoclastogenesis in rheumatoid synovium. We first examined the effect of interleukin-ll on the expression of receptor activator of NF-_κB ligand (RANKL), which is a critical protein for osteoclastogenesis, in rheumatoid synovial fibroblasts. Rheumatoid synovial fibroblasts expressed small amounts of RANKL mRNA, as assessed by RT-PCR analysis. IL-11 enhanced the RANKL expression at a concentration of 10 ng/ml. In contrast, IL-11 did not affect the production of osteoprotegerin (OPG), a decoy receptor for RANK. These results suggested that IL-11 might be involved in osteoclastogenesis in rheumatoid synovium via enhanced expression of RANKL in rheumatoid synovial cells. We next examined the effect of synovial T cells on osteoclastogenesis in rheumatoid synovium because synovial T cells are known to strongly express RANKL protein. We found that the co-culture of synovial macrophages and synovial T cells resulted in the generation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated giant cells (TRAP-MGCs), and that RANKL-mediated signaling may be partially involved in the generation of TRAP-MGCs. Although the generated TRAP-MGCs could not resorb a dentine, it is likely that these cells have the ability to differentiate to osteoclast. These findings provide new insights in the osteoclastogenesis in rheumatoid synovium.