TNFα blockade mediates bone protection in antigen-induced arthritis by reducing osteoclast precursor supply.

Uster, Stephanie Sarah; Matos Coelho, Fernanda; Aeberli, Daniel; Stein, Jens Volker; Hofstetter, Wilhelm; Engelhardt, Britta; Seitz, Michael (2018). TNFα blockade mediates bone protection in antigen-induced arthritis by reducing osteoclast precursor supply. Bone, 107, pp. 56-65. Elsevier 10.1016/j.bone.2017.10.020

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Bone protective effects of TNFα inhibition in rheumatoid arthritis are thought to be mediated by inhibiting synovial osteoclast differentiation and activity. However, it has not been addressed, if TNFα inhibitors alter the pool of peripheral osteoclast precursor cells (OPCs). Here, we blocked TNFα function in C57BL/6 mice with antigen induced arthritis (AIA) using the soluble TNFα 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 TNFα 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.

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