Department of Orthopaedic Surgery, University of California San Francisco, CA, USA.
Bone. 2010 Jun;46(6):1564-73. doi: 10.1016/j.bone.2010.02.014. Epub 2010 Feb 18.
The ability of bone to resist catastrophic failure is critically dependent upon the material properties of bone matrix, a composite of hydroxyapatite, collagen type I, and noncollagenous proteins. These properties include elastic modulus, hardness, and fracture toughness. Like other aspects of bone quality, matrix material properties are biologically-defined and can be disrupted in skeletal disease. While mineral and collagen have been investigated in greater detail, the contribution of noncollagenous proteins such as osteopontin to bone matrix material properties remains unclear. Several roles have been ascribed to osteopontin in bone, many of which have the potential to impact material properties. To elucidate the role of osteopontin in bone quality, we evaluated the structure, composition, and material properties of bone from osteopontin-deficient mice and wild-type littermates at several length scales. Most importantly, the results show that osteopontin deficiency causes a 30% decrease in fracture toughness, suggesting an important role for OPN in preventing crack propagation. This significant decline in fracture toughness is independent of changes in whole bone mass, structure, or matrix porosity. Using nanoindentation and quantitative backscattered electron imaging to evaluate osteopontin-deficient bone matrix at the micrometer level, we observed a significant reduction in elastic modulus and increased variability in calcium concentration. Matrix heterogeneity was also apparent at the ultrastructural level. In conclusion, we find that osteopontin is essential for the fracture toughness of bone, and reduced toughness in osteopontin-deficient bone may be related to the increased matrix heterogeneity observed at the micro-scale. By exploring the effects of osteopontin deficiency on bone matrix material properties, composition and organization, this study suggests that reduced fracture toughness is one mechanism by which loss of noncollagenous proteins contribute to bone fragility.
骨骼抵抗灾难性失效的能力主要取决于骨基质的材料特性，骨基质是由羟基磷灰石、I 型胶原和非胶原蛋白组成的复合材料。这些特性包括弹性模量、硬度和断裂韧性。与骨质量的其他方面一样，基质材料特性是生物学定义的，并且在骨骼疾病中会受到破坏。虽然已经对矿物质和胶原蛋白进行了更详细的研究，但骨基质材料特性中非胶原蛋白（如骨桥蛋白）的贡献仍不清楚。骨桥蛋白在骨骼中具有多种功能，其中许多功能可能会影响材料特性。为了阐明骨桥蛋白在骨质量中的作用，我们在几个长度尺度上评估了骨桥蛋白缺失小鼠和野生型同窝仔鼠的骨结构、组成和材料特性。最重要的是，结果表明骨桥蛋白缺失导致断裂韧性降低 30%，表明 OPN 在防止裂纹扩展中起重要作用。这种断裂韧性的显著下降与全骨量、结构或基质孔隙率的变化无关。使用纳米压痕和定量背散射电子成像技术在微米级评估骨桥蛋白缺失的骨基质，我们观察到弹性模量显著降低，钙浓度的变异性增加。在超微结构水平上，基质异质性也很明显。总之，我们发现骨桥蛋白对骨骼的断裂韧性至关重要，骨桥蛋白缺失的骨骼断裂韧性降低可能与在微尺度上观察到的基质异质性增加有关。通过探索骨桥蛋白缺失对骨基质材料特性、组成和组织的影响，本研究表明，断裂韧性降低是非胶原蛋白丢失导致骨骼脆弱的机制之一。
