Increased trabecular bone formation in mice lacking the growth factor midkine
| Autor: | F. Timo Beil, Philip Catala-Lehnen, Thomas Streichert, Thorsten Schinke, Anke Baranowsky, Robert P. Marshall, Anita Ignatius, Vincent Kanbach, Michael Amling, Takashi Muramatsu, Wolfgang Lehmann, Claudia Neunaber |
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| Rok vydání: | 2010 |
| Předmět: |
Aging
medicine.medical_specialty Genotype Ovariectomy Endocrinology Diabetes and Metabolism medicine.medical_treatment Osteoporosis Pleiotrophin Bone and Bones Bone resorption Mice Osteogenesis Internal medicine medicine Animals Orthopedics and Sports Medicine Bone Resorption Midkine Analysis of Variance Osteoblasts biology Growth factor Increased Bone Density Osteoblast Organ Size medicine.disease Phenotype medicine.anatomical_structure Endocrinology Gene Expression Regulation biology.protein Cytokines Female Cortical bone |
| Zdroj: | Journal of Bone and Mineral Research. 25:1724-1735 |
| ISSN: | 0884-0431 |
| DOI: | 10.1002/jbmr.75 |
| Popis: | 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 have previously analyzed Ptn-deficient mice but failed to detect any abnormality of skeletal development and remodeling. Together with the finding that Mdk expression increases in the course of primary osteoblast differentiation, we reasoned that Mdk, rather than Ptn, could play a physiologic role in bone formation. Here, we show that Mdk-deficient mice display an increased trabecular bone volume at 12 and 18 months of age, accompanied by cortical porosity. Histomorphometric quantification demonstrated an increased bone-formation rate compared with wild-type littermates, whereas bone resorption was differentially affected in trabecular and cortical bone of Mdk-deficient mice. To understand the effect of Mdk on bone formation at the molecular level, we performed a genome-wide expression analysis of primary osteoblasts and identified Ank and Enpp1 as Mdk-induced genes whose decreased expression in Mdk-deficient osteoblasts may explain, at least in part, the observed skeletal phenotype. Finally, we performed ovariectomy and observed bone loss only in wild-type but not in Mdk-deficient animals. Taken together, our data demonstrate that Mdk deficiency, at least in mice, results in an increased trabecular bone formation, thereby raising the possibility that Mdk-specific antagonists might prove beneficial in osteoporosis therapy. © 2010 American Society for Bone and Mineral Research |
| Databáze: | OpenAIRE |
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