Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response
Abstract 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 (rhTNF) at the frac...
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| Format: | Article |
| Language: | English |
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Springer Nature
2015-03-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201404487 |
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| _version_ | 1849332214902292480 |
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| author | James K Chan Graeme E Glass Adel Ersek Andrew Freidin Garry A Williams Kate Gowers Ana I Espirito Santo Rosemary Jeffery William R Otto Richard Poulsom Marc Feldmann Sara M Rankin Nicole J Horwood Jagdeep Nanchahal |
| author_facet | James K Chan Graeme E Glass Adel Ersek Andrew Freidin Garry A Williams Kate Gowers Ana I Espirito Santo Rosemary Jeffery William R Otto Richard Poulsom Marc Feldmann Sara M Rankin Nicole J Horwood Jagdeep Nanchahal |
| author_sort | James K Chan |
| collection | DOAJ |
| description | Abstract 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 (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF 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 rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 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 rhTNF 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. |
| format | Article |
| id | doaj-art-6b34ba89d64e4a4f9962c8a656576ff1 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2015-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-6b34ba89d64e4a4f9962c8a656576ff12025-08-20T03:46:16ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842015-03-017554756110.15252/emmm.201404487Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune responseJames K Chan0Graeme E Glass1Adel Ersek2Andrew Freidin3Garry A Williams4Kate Gowers5Ana I Espirito Santo6Rosemary Jeffery7William R Otto8Richard Poulsom9Marc Feldmann10Sara M Rankin11Nicole J Horwood12Jagdeep Nanchahal13Kennedy Institute of Rheumatology, University of OxfordKennedy Institute of Rheumatology, University of OxfordKennedy Institute of Rheumatology, University of OxfordKennedy Institute of Rheumatology, University of OxfordKennedy Institute of Rheumatology, University of OxfordNational Heart and Lung Institute, Imperial College LondonKennedy Institute of Rheumatology, University of OxfordHistopathology Laboratory and In Situ Hybridisation Service, Cancer Research UK – London Research InstituteHistopathology Laboratory and In Situ Hybridisation Service, Cancer Research UK – London Research InstituteHistopathology Laboratory and In Situ Hybridisation Service, Cancer Research UK – London Research InstituteKennedy Institute of Rheumatology, University of OxfordNational Heart and Lung Institute, Imperial College LondonKennedy Institute of Rheumatology, University of OxfordKennedy Institute of Rheumatology, University of OxfordAbstract 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 (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF 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 rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 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 rhTNF 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.https://doi.org/10.15252/emmm.201404487boneCCL2fractureinflammationTNF |
| spellingShingle | James K Chan Graeme E Glass Adel Ersek Andrew Freidin Garry A Williams Kate Gowers Ana I Espirito Santo Rosemary Jeffery William R Otto Richard Poulsom Marc Feldmann Sara M Rankin Nicole J Horwood Jagdeep Nanchahal Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response EMBO Molecular Medicine bone CCL2 fracture inflammation TNF |
| title | Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response |
| title_full | Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response |
| title_fullStr | Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response |
| title_full_unstemmed | Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response |
| title_short | Low‐dose TNF augments fracture healing in normal and osteoporotic bone by up‐regulating the innate immune response |
| title_sort | low dose tnf augments fracture healing in normal and osteoporotic bone by up regulating the innate immune response |
| topic | bone CCL2 fracture inflammation TNF |
| url | https://doi.org/10.15252/emmm.201404487 |
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