Osteoblast-Specific Krm2 Overexpression and Lrp5 Deficiency Have Different Effects on Fracture Healing in Mice
| العنوان: | Osteoblast-Specific Krm2 Overexpression and Lrp5 Deficiency Have Different Effects on Fracture Healing in Mice |
|---|---|
| المؤلفون: | Regina Ebert, Thorsten Schinke, Franz Jakob, Astrid Liedert, Ludger Klein-Hitpass, Viktoria Röntgen, Anita Ignatius, Jochen K. Lennerz, Michael Amling, Peggy Benisch |
| المصدر: | PLoS ONE, Vol 9, Iss 7, p e103250 (2014) PLoS ONE |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Osteopenia and Osteoporosis, Medizin, lcsh:Medicine, Bone remodeling, Mice, Cell Signaling, Osteogenesis, Fracture fixation, Medicine and Health Sciences, Biomechanics, Femur, lcsh:Science, Musculoskeletal System, Fracture Healing, Multidisciplinary, Lipoprotein receptor-related protein, Gene Expression Regulation, Developmental, LRP5, Osteoblast, Animal Models, medicine.anatomical_structure, Low Density Lipoprotein Receptor-Related Protein-5, Connective Tissue, Anatomy, Signal Transduction, Research Article, medicine.medical_specialty, Mouse Models, Bone healing, Biology, Research and Analysis Methods, Collagen Type I, Model Organisms, Osteoclast, Internal medicine, medicine, Animals, Humans, ddc:610, Bone, Osteoblasts, lcsh:R, Membrane Proteins, Biology and Life Sciences, Bone fracture, Cell Biology, medicine.disease, Collagen Type I, alpha 1 Chain, Endocrinology, Biological Tissue, Women's Health, lcsh:Q |
| الوصف: | The canonical Wnt/\textgreekb-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5 -/-) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5-/- mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5-/- mice, whereas osteoclast number was similarly increased in both genotypes in comparison with wild-type mice. Using microarray analysis we identified reduced expression of genes mainly involved in osteogenesis that seemed to be responsible for the observed stronger impairment of healing in Col1a1-Krm2 mice. In line with these findings, we detected decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active \textgreekb-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a significant role in regulating bone formation during fracture healing, antagonizing KRM2 might be a therapeutic option to improve fracture healing under compromised conditions, such as osteoporosis. \copyright 2014 Liedert et al. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1f2dc4838a5f3cac51903bf0abaa20b https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-115782 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b1f2dc4838a5f3cac51903bf0abaa20b |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |