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Medientyp:
E-Artikel
Titel:
Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model
Beteiligte:
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
Erschienen:
Springer Science and Business Media LLC, 2019
Erschienen in:Journal of Translational Medicine
Sprache:
Englisch
DOI:
10.1186/s12967-019-02171-4
ISSN:
1479-5876
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>