Citation

Bone protective effects of TNF inhibition in rheumatoid arthritis are thought to be mediated by inhibiting synovial osteoclast differentiation and activity. However, it has not been addressed, if TNF inhibitors alter the pool of peripheral osteoclast precursor cells (OPCs). Here, we blocked TNF function in C57BL/6 mice with antigen induced arthritis (AIA) using the soluble TNF receptor etanercept. Synovial bone lesions and osteoclasts were markedly reduced upon Etanercept in the early chronic phase of AIA. Unexpectedly this was not associated with a reduced recruitment of circulating OPCs to the arthritic joint nor to reduced synovial inflammation. In contrast we found that OPC numbers in bone marrow and blood were significantly reduced. Overall our study suggests that arrest of osteoclast mediated bone lesions upon inhibition of TNF is, at least initially, based on reduced OPC availability in the periphery, and not on OPC recruitment or local anti-inflammatory effects in the arthritic joint.