Silva Matthew J, Brodt Michael D, Wopenka Brigitte, Thomopoulos Stavros, Williams Derek, Wassen Maurice H M, Ko Mike, Kusano Nozomu, Bank Ruud A
Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University, St Louis, Missouri 63110, USA.
J Bone Miner Res. 2006 Jan;21(1):78-88. doi: 10.1359/JBMR.050909. Epub 2005 Sep 19.
To examine the link between bone material properties and skeletal fragility, we analyzed the mechanical, histological, biochemical, and spectroscopic properties of bones from a murine model of skeletal fragility (SAMP6). Intact bones from SAMP6 mice are weak and brittle compared with SAMR1 controls, a defect attributed to reduced strength of the bone matrix. The matrix weakness is attributed primarily to poorer organization of collagen fibers and reduced collagen content.
The contribution of age-related changes in tissue material properties to skeletal fragility is poorly understood. We previously reported that bones from SAMP6 mice are weak and brittle versus age-matched controls. Our present objectives were to use the SAMP6 mouse to assess bone material properties in a model of skeletal fragility and to relate defects in the mechanical properties of bone to the properties of demineralized bone and to the structure and organization of collagen and mineral.
Femora from 4- and 12-month-old SAMR1 (control) and SAMP6 mice were analyzed using bending and torsional mechanical testing of intact bones, tensile testing of demineralized bone, quantitative histology (including collagen fiber orientation), collagen cross-links biochemistry, and Raman spectroscopic analysis of mineral and collagen.
Intact bones from SAMP6 mice have normal elastic properties but inferior failure properties, with 60% lower fracture energy versus SAMR1 controls. The strength defect in SAMP6 bones was associated with a 23% reduction in demineralized bone strength, which in turn was associated with poorer collagen fiber organization, lower collagen content, and higher hydroxylysine levels. However, SAMP6 have normal levels of collagen cross-links and normal apatite mineral structure.
Bones from SAMP6 osteoporotic mice are weak and brittle because of a defect in the strength of the bone matrix. This defect is attributed primarily to poorer organization of collagen fibers and reduced collagen content. These findings highlight the role of the collagen component of the bone matrix in influencing skeletal fragility.
为研究骨材料特性与骨骼脆性之间的联系，我们分析了骨骼脆性小鼠模型（SAMP6）骨骼的力学、组织学、生物化学和光谱特性。与SAMR1对照小鼠相比，SAMP6小鼠的完整骨骼脆弱易碎，这种缺陷归因于骨基质强度降低。基质薄弱主要归因于胶原纤维排列较差和胶原含量减少。
与年龄相关的组织材料特性变化对骨骼脆性的影响尚不清楚。我们之前报道过，与年龄匹配的对照小鼠相比，SAMP6小鼠的骨骼脆弱易碎。我们目前的目标是利用SAMP6小鼠评估骨骼脆性模型中的骨材料特性，并将骨力学性能缺陷与脱矿骨特性以及胶原和矿物质的结构与排列联系起来。
对4个月和12个月大的SAMR1（对照）和SAMP6小鼠的股骨进行分析，采用完整骨骼的弯曲和扭转力学测试、脱矿骨的拉伸测试、定量组织学（包括胶原纤维取向）、胶原交联生物化学以及矿物质和胶原的拉曼光谱分析。
SAMP6小鼠的完整骨骼具有正常的弹性特性，但破坏性能较差，与SAMR1对照小鼠相比，骨折能量低60%。SAMP6骨骼的强度缺陷与脱矿骨强度降低23%有关，而这又与胶原纤维排列较差、胶原含量较低和羟赖氨酸水平较高有关。然而，SAMP6小鼠的胶原交联水平正常，磷灰石矿物质结构正常。
SAMP6骨质疏松小鼠的骨骼脆弱易碎是由于骨基质强度缺陷。这种缺陷主要归因于胶原纤维排列较差和胶原含量减少。这些发现突出了骨基质胶原成分在影响骨骼脆性方面的作用。
