Backgrounds: In rheumatoid arthritis, significant synovial inflammation eventually leads to destruction of the bone caused by osteoclasts in pannus. It is not entirely clear whether the osteoclast precursors seen in pannus arises from division of local precursors or differentiation from newly recruited blood monocytes.
Objective: To identify the origin of osteoclasts in pannus in arthritis.
Methods: Osteoclast precursors were identified by RANKL-induced osteoclastogenesis in vitro using joint tissues of collagen-induced arthritic mice. Irradiated wild-type (WT) DBA1/J mice were transplanted with bone marrow cells from TRAP-Tdtomato transgenic mice. WT and TRAP-Tdtomato transgenic mice were conjoined for parabiosis. The transplanted mice and parabionts were subjected to the development of collagen-induced arthritis. Flow cytometry analysis, immunohistochemistry, and two-photon microscopy imaging in vivo were applied to discern whether osteoclast precursors and osteoclasts were originated from bone marrow through circulation or not.
Results: Immunohistochemistry analysis of arthritic knees of bone marrow chimeric mice showed that the osteoclasts in pannus were Tdtomato+ and exclusively derived from bone marrow. 55% of osteoclasts in pannus were Tdtomato+ in WT parabionts, which was consistent with the replacement rate of monocytes in blood and osteoclast precursors in joint tissues. In vivo imaging of the bone marrow using two-photon microscopy showed the increased motility of osteoclast precursors, which was 1.00 ± 0.04 μm/min in WT mice and 1.45 ± 0.06 μm/min in arthritic mice (p < 0.0001), some of them entering the blood stream.
Conclusion: Osteoclasts in pannus in collagen-induced arthritis are exclusively derived from monocytes in bone marrow through circulation.