Increased susceptibility to microdamage in Brtl/+ mouse model for osteogenesis imperfecta
Increased susceptibility to microdamage in Brtl/+ mouse model for osteogenesis imperfecta
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DOI：
10.1016/j.bone.2011.12.007
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发表时间：
2012-03-01
期刊：
影响因子：
4.1
通讯作者：
Kozloff, Kenneth M.
中科院分区：
文献类型：
--
作者：
Davis, Mathieu S.;Kovacic, Bethany L.;Kozloff, Kenneth M.
骨生成障碍（OI）是一种胶原或胶原相关蛋白的遗传性疾病，对骨量和抗骨折能力产生不利影响。关于微损伤在OI中所起的作用以及OI骨是否比胶原未受影响的骨更容易损伤累积，我们知之甚少。Brt 1/+小鼠是OI的杂合模型，其在一个COL 1A 1等位基因中含有Gly 349 Cys取代，并表现出低延展性表型。在8周大的时候。Brt 1/+显示破骨细胞数量增加，这模拟了经常在OI患者中发现的上调的骨转换。我们推测Brt 1/+中破骨细胞活性的上调部分是由于与微损伤修复相关的重塑增加。在本研究中，我们使用Brt 1/+来研究OI骨对微损伤的敏感性。使用小鼠尺骨负荷模型来诱导微损伤并检验Brt 1/+比年龄匹配的野生型（WT）对应物更易受损伤累积的假设。线弹性断裂力学（LEFM）被用来研究Brt 1/+和WT骨的断裂韧性性质，以确定是否有任何相关性与韧性和程度的microdamage.Results结果表明，Brt 1/+ ulcerative受到正常笼活动表现出固有的更大量的微损伤比WT控制。在轴向压缩载荷后，Brt 1/+骨水泥比WT对应物更容易损坏，尽管表现出对全骨变形的更大抵抗力。断裂韧性结果表明，Brt 1/+试样，尽管没有表现出显着的差异，显示出更低的断裂韧性值比他们的WT对应的趋势。相关性表明，随着断裂韧性的降低，微观损伤水平往往会增加。总之，这些发现可能具有很强的临床意义，解释增加的脆性和重塑活动的OI患者。(C)2011 Elsevier Inc. All rights reserved.
Osteogenesis imperfecta (OI) is a genetic disease of collagen or collagen-related proteins that adversely impacts bone mass and fracture resistance. Little is known regarding the role that microdamage plays in OI and whether or not OI bone is more prone to damage accumulation than bone with unaffected collagen. The Brtl/+ mouse is a heterozygous model for OI which contains a Gly349Cys substitution in one COL1A1 allele, and demonstrates a low ductility phenotype. At 8 weeks of age. Brtl/+ demonstrates an increase in osteoclast number, which mimics the upregulated bone turnover often found in OI patients. We hypothesize that upregulated osteoclast activity in Brtl/+ is due, in part, to increased remodeling associated with microdamage repair. In the present study, we used Brtl/+ to investigate the susceptibility of OI bone to microdamage. The mouse ulnar loading model was used to induce microdamage and to test the hypothesis that Brtl/+ is more susceptible to damage accumulation than age-matched wild type (WT) counterparts. Linear elastic fracture mechanics (LEFM) was used to investigate the fracture toughness properties of both Brtl/+ and WT bones to determine if there is any correlation with toughness and the degree of microdamage.Results show that Brtl/+ ulnae subject to normal cage activity demonstrate an inherently larger amount of microdamage than WT controls. Following axial compressive loading, Brtl/+ ulnae are more prone to damage than WT counterparts despite demonstrating a greater resistance to whole-bone deformation. Fracture toughness results demonstrate that Brtl/+ specimens, despite not exhibiting a significant difference, display a trend toward lower fracture toughness values than their WT counterparts. Correlations show that microdamage levels tend to increase as fracture toughness decreases. Together, these findings may have strong clinical implications for explaining increased fragility and remodeling activity in OI patients. (C) 2011 Elsevier Inc. All rights reserved.