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- Title
Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model.
- Authors
Wagner, Johannes M.; Schmidt, Sonja V.; Dadras, Mehran; Huber, Julika; Wallner, Christoph; Dittfeld, Stephanie; Becerikli, Mustafa; Jaurich, Henriette; Reinkemeier, Felix; Drysch, Marius; Lehnhardt, Marcus; Behr, Björn
- Abstract
<bold>Background: </bold>Delayed bone healing, especially in long bones poses one of the biggest problems in orthopeadic and reconstructive surgery and causes tremendous costs every year. There is a need for exploring the causes in order to find an adequate therapy. Earlier investigations of human scaphoid non-union revealed an elevated osteoclast activity, accompanied by upregulated levels of TGF-beta and RANKL. Interestingly, scaphoid non-union seemed to be well vascularized.<bold>Methods: </bold>In the current study, we used a murine femur-defect model to study atrophic non unions over a time-course of 10 weeks. Different time points were chosen, to gather insights into the dynamic processes of non-union establishment.<bold>Results: </bold>Histological analyses as well as western blots and qRT-PCR indicated enhanced osteoclast activity throughout the observation period, paralleled by elevated levels of TGF-beta, TNF-alpha, MMP9, MMP13 and RANKL, especially during the early phases of non-union establishment. Interestingly, elevated levels of these mediators decreased markedly over a period of 10 weeks, as inflammatory reaction during non-union establishment seemed to wear out. To our surprise, osteoblastogenesis seemed to be unaffected during early stages of non-union establishment.<bold>Conclusion: </bold>Taken together, we gained first insights into the establishment process of atrophic non unions, in which inflammatory processes accompanied by highly elevated osteoclast activity seem to play a leading role.
- Subjects
INFLAMMATION; OSTEOCLASTS; WESTERN immunoblotting; PLASTIC surgery; HEALING; ANIMAL experimentation; BIOLOGICAL models; CELL physiology; CELL receptors; COMPARATIVE studies; CYTOKINES; UNUNITED fractures; INFLAMMATORY mediators; MACROPHAGES; RESEARCH methodology; MEDICAL cooperation; MEMBRANE proteins; MICE; RESEARCH; EVALUATION research; ATROPHY; OSTEOBLASTS
- Publication
Journal of Translational Medicine, 2019, Vol 17, Issue 1, p1
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-019-02171-4