BoneKEy Reports | BoneKEy Watch
Novel osteoclast precursor with a role in rheumatoid arthritis
DOI:10.1038/bonekey.2013.30
By comparing cells from the bone marrow of wild-type mice with SKG mice, which represent an established model of rheumatoid arthritis (RA), Charles et al. have identified a specific subset of cells that act as osteoclast precursors (OCPs). CD11b−/loLy6Chi cells behave as OCPs in vivo and in vitro, differentiating into osteoclasts. They also increase in SKG mice 8 weeks after an injection of zymosan, given to stimulate the innate immune system, initiates RA in this model. CD11b−/loLy6Chi cells are also different from cells in the myeloid lineage that have been previously characterized.
The most startling finding was obtained by adoptive transfer of the CD11b−/loLy6Chi cells into Rag2−/− mice. These animals normally develop an inflammatory arthritis around 4 weeks after adoptive transfer of CD4+CD25− T cells from SKG mice, but transfer of CD11b−/loLy6Chi cells led to a significant reduction of arthritis activity, evidenced by decreased joint inflammation in the recipients.
Further analysis revealed that the CD11b−/loLy6Chi cells increased nitric oxide production and suppressed the proliferation of CD4+ and CD8− cells.
Editor’s comment: The authors have identified bone-marrow CD11b−/loLy6Chi cells as osteoclast precursors with T-cell suppressive activity. Because these cells are expanded in inflammatory arthritis, suppression of differentiation of these cells into osteoclasts can inhibit bone resorption and increase T-cell suppressive activity. Further elucidation of the regulation of these cell populations may give us a clue as to how to simultaneously control bone loss and inflammation.
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