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

	Text 1-s2.0-S8756328217303861-main.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (2MB)
	Text BONE_paper_Stephanie_Uster.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (3MB)

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.

Interest & Impact

Downloads

87 since deposited on 23 Feb 2018
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item