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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Knochenbiologie & Orthopädische Forschung

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
09 Interdisciplinary Units > Microscopy Imaging Center MIC

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Uster, Stephanie Sarah; Matos Coelho, Fernanda; Aeberli, Daniel; Stein, Jens Volker; Hofstetter, Wilhelm; Engelhardt, Britta and Seitz, Michael

Subjects:

600 Technology > 610 Medicine & health

ISSN:

8756-3282

Publisher:

Elsevier

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

23 Feb 2018 13:32

Last Modified:

24 Oct 2019 09:04

Publisher DOI:

10.1016/j.bone.2017.10.020

PubMed ID:

29081378

Uncontrolled Keywords:

Arthritis Blockade of TNFα Bone protection Osteoclast precursors

BORIS DOI:

10.7892/boris.108237

URI:

https://boris.unibe.ch/id/eprint/108237

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