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Bone Abstracts (2014) 3 PP46 | DOI: 10.1530/boneabs.3.PP46

Bone development/growth and fracture repair

Midkine deficiency significantly delayed chondrogenesis during fracture healing in mice

Melanie Haffner-Luntzer1, Aline Heilmann1, Anna Rapp1, Thorsten Schinke2, Michael Amling2, Anita Ignatius1 & Astrid Liedert1

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1Department of Orthopaedic Research and Biomechanics, Ulm, Germany; 2Department of Osteology and Biomechanics, Hamburg, Germany.


One growth factor that potentially plays a role in fracture healing is midkine (Mdk). Mdk is expressed in chondrocytes during bone repair (Ohta et al. 1999) and has been shown to influence bone mass and mechanotransduction (Neunaber et al. 2010, Liedert et al. 2011). The aim of the present study was to evaluate the effects of Mdk-deficiency on bone repair in a standardized mouse femur osteotomy model.

Mdk-deficient and wildtype mice (C57BL/6) were used for the study. After induction of a femur osteotomy stabilized with an external fixator, mice were sacrificed at day 10 or 21 and fracture healing was assessed by three-point-bending test, microCT based evaluation and histomorphometry. Furthermore, immunohistochemical staining for β-catenin was performed.

Mdk−/− mice displayed a significantly decreased flexural rigidity of the fractured femur 21 days post-surgery. MicroCT data indicated that bone mineral density in the periosteal callus in Mdk-deficient mice did not differ significantly from WT littermates. The moment of inertia in the bending axis was significantly reduced in animals lacking Mdk indicating an altered callus geometry during fracture healing. We observed that Mdk-deficient mice showed a significantly decreased amount of cartilage in the callus after 10 days, whereas the cartilage content was significantly increased after 21 days. The expression level of β-catenin was lower in Mdk−/− mice 10 days after fracture.

Our data indicate an impaired fracture healing due to a delayed chondrogenesis in Mdk-deficient mice. Together with the finding that a chondrogenic cell line overexpressing Mdk displays enhanced chondrogenesis (Ohta et al. 1999), we hypthothesize that Mdk plays a pivotal role in the development of cartilage tissue in the early fracture callus.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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