Bone morphogenetic protein signaling through ACVR1 and BMPR1A negatively regulates bone mass along with alterations in bone composition
| Autor: | Yuji Mishina, Gurjit S. Mandair, Ryan Ridella, Michael D. Morris, Yanshuai Zhang, Hongchen Sun, Ce Shi, David H. Kohn, Akira Takahashi, Gloria VanRenterghem, Honghao Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Bone morphogenetic protein 8A 030209 endocrinology & metabolism Spectrum Analysis Raman Bone morphogenetic protein Bone morphogenetic protein 2 Article Bone remodeling 03 medical and health sciences 0302 clinical medicine Bone Density Structural Biology medicine Animals Femur Bone Morphogenetic Protein Receptors Type I Mice Knockout Osteoblasts Chemistry Osteoblast X-Ray Microtomography Cell biology Bone morphogenetic protein 7 Bone morphogenetic protein 6 030104 developmental biology Bone morphogenetic protein 5 medicine.anatomical_structure Cancellous Bone Female Collagen Activin Receptors Type I Signal Transduction |
| Zdroj: | Journal of Structural Biology. 201:237-246 |
| ISSN: | 1047-8477 |
| Popis: | Bone quantity and bone quality are important factors in determining the properties and the mechanical functions of bone. This study examined the effects of disrupting bone morphogenetic protein (BMP) signaling through BMP receptors on bone quantity and bone quality. More specifically, we disrupted two BMP receptors, Acvr1 and Bmpr1a, respectively, in Osterix-expressing osteogenic progenitor cells in mice. We examined the structural changes to the femora from 3-month old male and female conditional knockout (cKO) mice using micro-computed tomography (micro-CT) and histology, as well as compositional changes to both cortical and trabecular compartments of bone using Raman spectroscopy. We found that the deletion of Acvr1 and Bmpr1a, respectively, in an osteoblast-specific manner resulted in higher bone mass in the trabecular compartment. Disruption of Bmpr1a resulted in a more significantly increased bone mass in the trabecular compartment. We also found that these cKO mice showed lower mineral-to-matrix ratio, while tissue mineral density was lower in the cortical compartment. Collagen crosslink ratio was higher in both cortical and trabecular compartments of male cKO mice. Our study suggested that BMP signaling in osteoblast mediated by BMP receptors, namely ACVR1 and BMPR1A, is critical in regulating bone quantity and bone quality. |
| Databáze: | OpenAIRE |
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