gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019)

22. - 25.10.2019, Berlin

Impaired bone regeneration in αCGRP-deficient mice

Meeting Abstract

  • presenting/speaker Jessika Appelt - Center for Musculoskeletal Surgery, Julius Wolff Institut, Charité - Universitätsmedizin, Berlin, Germany
  • Denise Jahn - Center for Musculoskeletal Surgery, Julius Wolff Institut, Charité - Universitätsmedizin, Berlin, Germany
  • Melanie Fuchs - Center for Musculoskeletal Surgery, Julius Wolff Institut, Charité - Universitätsmedizin, Berlin, Germany
  • Alina Bahn - Center for Musculoskeletal Surgery, Julius Wolff Institut, Charité - Universitätsmedizin, Berlin, Germany
  • Michael Amling - Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Serafeim Tsitsilonis - Center for Musculoskeletal Surgery, Julius Wolff Institut, Charité-Universitätsmedizin (Berlin), Berlin Institute of Health (BIH), Berlin, Germany
  • Johannes Keller - Center for Musculoskeletal Surgery, Julius Wolff Institut, Charité-Universitätsmedizin (Berlin), Berlin Institute of Health (BIH), Berlin, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2019). Berlin, 22.-25.10.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocAB28-791

doi: 10.3205/19dkou162, urn:nbn:de:0183-19dkou1628

Veröffentlicht: 22. Oktober 2019

© 2019 Appelt et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: Impaired fracture healing, including delayed unions and non-unions, still represents an ongoing clinical challenge causing high socioeconomic costs. Complications of the delayed healing process are recurrent surgeries, immobilization and chronic pain, which deeply affects patients' quality of life. Current treatment options are limited due to insufficient understanding of the mechanisms governing bone regeneration. In this regard, the neuropeptide calcitonin gene related peptide alpha (αCGRP) caught our interest. This neuropeptide, encoded by the gene Calca, is known to stimulate bone formation by osteoblasts and was suggested to support bone healing. Specifically, bone regeneration aided by magnesium implants showed increased αCGRP levels in the newly forming bone. However, the exact function of endogenous αCGRP in bone healing is still unknown. Therefore, our study aims at unraveling the role of αCGRP during bone regeneration and to translate the findings into therapies for impaired bone healing.

Methods: Bone healing in wild-type (WT) and αCGRP-deficient mice was analyzed over 21 days. The animals were operated using a standardised femoral osteotomy model. The fracture was stabilised with an external fixator. After 7, 14 and 21 days bone regeneration was evaluated by μCT analysis and histomorphometry, whereby callus formation was characterised through assessment of bone (BV)-and tissue volume (TV). All animal experiments were approved by the responsible authories and conducted in accordance with the German Animal Welfare Act.

Results and conclusion: Overall, a statistical significant, negative impact of the loss of αCGRP on bone regeneration was revealed. In detail, a significantly decreased BV and TV in the callus of αCGRP-deficient mice compared to WT controls was observed 14 and 21 days post-operation. Additionally, 21 days after trauma, impaired bone bridging was noticed in αCGRP-deficient mice, whereas full bridging was present in WT littermates. Together, these data demonstrate a reduced healing capacity in αCGRP-deficient mice and highlight the importance of the neuropeptide αCGRP during bone regeneration. In conclusion, this warrants further mechanistic studies, as the identification of involved signaling pathways may aid in the development of novel therapies for impaired bone healing.