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BMC Musculoskeletal Disorders

, 15:184

Pathophysiology of musculoskeletal disorders

Abstract

BackgroundThe overexpression of tumor necrosis factor TNF-α leads to systemic as well as local loss of bone and cartilage and is also an important regulator during fracture healing. In this study, we investigate how TNF-α inhibition using a targeted monoclonal antibody affects fracture healing in a TNF-α driven animal model of human rheumatoid arthritis RA and elucidate the question whether enduring the anti TNF-α therapy after trauma is beneficial or not.

MethodsA standardized femur fracture was applied to wild type and human TNF-α transgenic mice hTNFtg mice, which develop an RA-like chronic polyarthritis. hTNFtg animals were treated with anti-TNF antibody Infliximab during the fracture repair. Untreated animals served as controls. Fracture healing was evaluated after 14 and 28 days of treatment by clinical assessment, biomechanical testing and histomorphometry.

ResultsHigh levels of TNF-α influence fracture healing negatively, lead to reduced cartilage and more soft tissue in the callus as well as decreased biomechanical bone stability. Blocking TNF-α in hTNFtg mice lead to similar biomechanical and histomorphometrical properties as in wild type.

ConclusionsHigh levels of TNF-α during chronic inflammation have a negative impact on fracture healing. Our data suggest that TNF-α inhibition by an anti-TNF antibody does not interfere with fracture healing.

KeywordsAnti-TNFα Inflammation Fracture healing Rheumatoid arthritis Treatment AbbreviationsTNF-αTumor necrosis factor alpha

RARheumatoid arthritis

hTNFtgMice with a human TNF alpha transgenic background

ILInterleukin

TNFiAntiTNFalpha antibody treatment

MSCMesenchymal stem cell

AOIArea of interest.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2474-15-184 contains supplementary material, which is available to authorized users.

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Autor: Melanie Timmen - Heriburg Hidding - Britta Wieskötter - Wolfgang Baum - Thomas Pap - Michael J Raschke - Georg Schett - J

Fuente: https://link.springer.com/







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