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Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response.

Chan JK, Glass GE, Ersek A, Freidin A, Williams GA, Gowers K, Espirito Santo AI, Jeffery R, Otto WR, Poulsom R, Feldmann M, Rankin SM, Horwood NJ, Nanchahal J - EMBO Mol Med (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.

No MeSH data available.


Related in: MedlinePlus

Definition of the early fracture healing pathwaySchematic detailing the role of the early inflammatory pathway in fracture healing. Addition of local rhTNF promotes the recruitment of neutrophils and monocytes via up-regulation of CCL2, leading to augmentation of fracture repair.
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fig06: Definition of the early fracture healing pathwaySchematic detailing the role of the early inflammatory pathway in fracture healing. Addition of local rhTNF promotes the recruitment of neutrophils and monocytes via up-regulation of CCL2, leading to augmentation of fracture repair.

Mentions: In summary, our combined in vivo and in vitro data show that addition of low-dose rhTNF during the early inflammatory response promotes the recruitment of neutrophils and monocytes via up-regulation of CCL2 and leads to acceleration of fracture repair. Our data show that the role of neutrophils is not simply limited to clearance of pathogens and cellular debris. They also orchestrate the next stage of resolution and regeneration through the recruitment of monocytes. Mechanistically our data suggest that local administration of a low dose of recombinant TNF at the fracture site shortly after injury acts via two mechanisms. Firstly, it potentiates and augments the early innate immune response comprising neutrophils followed by monocyte/macrophage recruitment to promote the physiological healing processes through the CCL2/CCR2 axis (Fig6). Secondly, it promotes the recruitment and osteogenic differentiation of MSCs (Glass et al, 2011).


Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response.

Chan JK, Glass GE, Ersek A, Freidin A, Williams GA, Gowers K, Espirito Santo AI, Jeffery R, Otto WR, Poulsom R, Feldmann M, Rankin SM, Horwood NJ, Nanchahal J - EMBO Mol Med (2015)

Definition of the early fracture healing pathwaySchematic detailing the role of the early inflammatory pathway in fracture healing. Addition of local rhTNF promotes the recruitment of neutrophils and monocytes via up-regulation of CCL2, leading to augmentation of fracture repair.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492816&req=5

fig06: Definition of the early fracture healing pathwaySchematic detailing the role of the early inflammatory pathway in fracture healing. Addition of local rhTNF promotes the recruitment of neutrophils and monocytes via up-regulation of CCL2, leading to augmentation of fracture repair.
Mentions: In summary, our combined in vivo and in vitro data show that addition of low-dose rhTNF during the early inflammatory response promotes the recruitment of neutrophils and monocytes via up-regulation of CCL2 and leads to acceleration of fracture repair. Our data show that the role of neutrophils is not simply limited to clearance of pathogens and cellular debris. They also orchestrate the next stage of resolution and regeneration through the recruitment of monocytes. Mechanistically our data suggest that local administration of a low dose of recombinant TNF at the fracture site shortly after injury acts via two mechanisms. Firstly, it potentiates and augments the early innate immune response comprising neutrophils followed by monocyte/macrophage recruitment to promote the physiological healing processes through the CCL2/CCR2 axis (Fig6). Secondly, it promotes the recruitment and osteogenic differentiation of MSCs (Glass et al, 2011).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.

No MeSH data available.


Related in: MedlinePlus