Increased trabecular bone formation in mice lacking the growth factor midkine

• DOI: 10.1002/jbmr.75
• Publication Date: 2010-02-23T15:36:19Z
• Authors: Claudia Neunaber; Philip Catala-Lehnen; F Timo Beil; Robert P Marshall; Vincent Kanbach; Anke Baranowsky; Wolfgang Lehmann; Thomas Streichert; Anita Ignatius; Takashi Muramatsu; Thorsten Schinke; Michael Amling
• Keywords: Midkine; Pleiotrophin

Midkine (Mdk) and pleiotrophin (Ptn) comprise a family of heparin-binding growth factors known primarily for their effects on neuronal cells. Since transgenic mice overexpressing Ptn have been reported to display increased bone density, we previously analyzed Ptn-deficient but failed detect any abnormality skeletal development remodeling. Together with the finding that Mdk expression increases in course primary osteoblast differentiation, reasoned Mdk, rather than Ptn, could play physiologic role formation. Here, show Mdk-deficient an trabecular volume at 12 18 months age, accompanied by cortical porosity. Histomorphometric quantification demonstrated bone-formation rate compared wild-type littermates, whereas resorption was differentially affected mice. To understand effect formation molecular level, performed genome-wide analysis osteoblasts identified Ank Enpp1 as Mdk-induced genes whose decreased may explain, least part, observed phenotype. Finally, ovariectomy loss only not animals. Taken together, our data demonstrate deficiency, mice, results formation, thereby raising possibility Mdk-specific antagonists might prove beneficial osteoporosis therapy.