Balooch Guive, Balooch Mehdi, Nalla Ravi K, Schilling Stephen, Filvaroff Ellen H, Marshall Grayson W, Marshall Sally J, Ritchie Robert O, Derynck Rik, Alliston Tamara
Graduate Program in Oral and Craniofacial Sciences, Departments of Preventive and Restorative Dental Sciences and Cell and Tissue Biology, and Programs in Cell Biology and Development, University of California, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18813-8. doi: 10.1073/pnas.0507417102. Epub 2005 Dec 14.
The characteristic toughness and strength of bone result from the nature of bone matrix, the mineralized extracellular matrix produced by osteoblasts. The mechanical properties and composition of bone matrix, along with bone mass and architecture, are critical determinants of a bone's ability to resist fracture. Several regulators of bone mass and architecture have been identified, but factors that regulate the mechanical properties and composition of bone matrix are largely unknown. We used a combination of high-resolution approaches, including atomic-force microscopy, x-ray tomography, and Raman microspectroscopy, to assess the properties of bone matrix independently of bone mass and architecture. Properties were evaluated in genetically modified mice with differing levels of TGF-beta signaling. Bone matrix properties correlated with the level of TGF-beta signaling. Smad3+/- mice had increased bone mass and matrix properties, suggesting that the osteopenic Smad3-/- phenotype may be, in part, secondary to systemic effects of Smad3 deletion. Thus, a reduction in TGF-beta signaling, through its effector Smad3, enhanced the mechanical properties and mineral concentration of the bone matrix, as well as the bone mass, enabling the bone to better resist fracture. Our results provide evidence that bone matrix properties are controlled by growth factor signaling.
骨骼特有的韧性和强度源于骨基质的特性，骨基质是成骨细胞产生的矿化细胞外基质。骨基质的力学性能和组成，以及骨量和结构，是骨骼抗骨折能力的关键决定因素。虽然已经确定了几种调节骨量和结构的因子，但调节骨基质力学性能和组成的因素在很大程度上仍不清楚。我们采用了包括原子力显微镜、X射线断层扫描和拉曼光谱在内的高分辨率方法组合，以独立于骨量和结构来评估骨基质的特性。在具有不同TGF-β信号水平的转基因小鼠中评估了这些特性。骨基质特性与TGF-β信号水平相关。Smad3+/-小鼠的骨量和基质特性增加，这表明骨质减少的Smad3-/-表型可能部分继发于Smad3缺失的全身效应。因此，通过其效应因子Smad3减少TGF-β信号传导，增强了骨基质的力学性能和矿物质浓度以及骨量，使骨骼能够更好地抵抗骨折。我们的结果提供了证据表明骨基质特性受生长因子信号传导控制。
