Bone morphogenetic protein signaling through ACVR1 and BMPR1A negatively regulates bone mass along with alterations in bone composition |
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Authors: | Ce Shi Gurjit S Mandair Honghao Zhang Gloria G Vanrenterghem Ryan Ridella Akira Takahashi Yanshuai Zhang David H Kohn Michael D Morris Yuji Mishina Hongchen Sun |
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Institution: | 1. Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, 1500 Qinghua Road, Changchun 130000, China;2. Department of Biologic and Materials Sciences, University of Michigan, School of Dentistry, 1011 N. University Avenue, Ann Arbor, MI 48109-1078, USA;3. Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48108-1055, USA;4. Biomedical Engineering College of Engineering, University of Michigan, MI 48109-2110, USA |
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Abstract: | 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. |
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Keywords: | Bone quantity Bone quality Micro-CT Raman spectroscopy BMP receptor Bone composition |
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