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.
17 May 2014 - 20 May 2014