Open AccessLow‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response
Author(s) -
Chan James K,
Glass Graeme E,
Ersek Adel,
Freidin Andrew,
Williams Garry A,
Gowers Kate,
Espirito Santo Ana I,
Jeffery Rosemary,
Otto William R,
Poulsom Richard,
Feldmann Marc,
Rankin Sara M,
Horwood Nicole J,
Nanchahal Jagdeep
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404487
Subject(s) - bone healing , medicine , inflammation , chemokine , tumor necrosis factor alpha , innate immune system , wound healing , immunology , osteoporosis , immune system , surgery
The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low‐dose recombinant human TNF (rh TNF ) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rh TNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti‐ TNF impaired fracture healing. Addition of rh TNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL 2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR 2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rh TNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization.