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Deletion of Coagulation Factor IX Compromises Bone Mass and Strength: Murine Model of Hemophilia B (Christmas Disease)
Calcified Tissue International ( IF 3.3 ) Pub Date : 2021-06-12 , DOI: 10.1007/s00223-021-00872-x
Emily A Larson 1 , Hillary J Larson 1 , Jason A Taylor 2 , Robert F Klein 3, 4
Affiliation  

Osteopenia and osteoporosis have increasingly become a recognized morbidity in those persons with hemophilia (PwH) receiving inadequate prophylactic clotting factor replacement. Animal models can control or eliminate genetic and environmental factors and allow for invasive testing not clinically permissible. Here, we describe the skeletal phenotype of juvenile and adult male mice with a genetically engineered deficiency in coagulation factor IX (FIX KO). Although the somatic growth of FIX KO mice matched that of their wild-type (WT) littermates at 10 and 20 weeks of age, the FIX KO mice displayed reduced bone mineral density (BMD), reduced cortical and cancellous bone mass, and diminished whole bone fracture resistance. These findings coupled with parallel observations in a murine model of hemophilia A (FVIII deficiency) point to an effector downstream of the coagulation cascade that is necessary for normal skeletal development. Further study of potential mechanisms underlying the bone disease observed in rare clotting factor deficiency syndromes may lead to new diagnostic and therapeutic insights for metabolic bone diseases in general.



中文翻译:

凝血因子 IX 的删除会影响骨量和强度:血友病 B(圣诞病)的鼠模型

骨质减少和骨质疏松症越来越成为血友病 (PwH) 患者预防性凝血因子替代治疗不足的一种公认疾病。动物模型可以控制或消除遗传和环境因素,并允许进行临床上不允许的侵入性测试。在这里,我们描述了具有凝血因子 IX (FIX KO) 基因工程缺陷的幼年和成年雄性小鼠的骨骼表型。虽然 FIX KO 小鼠的体细胞生长与其野生型 (WT) 同窝仔鼠在 10 和 20 周龄时相匹配,但 FIX KO 小鼠显示出骨矿物质密度 (BMD) 降低、皮质骨和松质骨量减少以及整体骨量减少。抗骨折能力。这些发现与 A 型血友病(FVIII 缺陷)鼠模型中的平行观察结果相结合,表明凝血级联下游的效应子是正常骨骼发育所必需的。对罕见凝血因子缺乏综合征中观察到的骨病潜在机制的进一步研究可能会为一般代谢性骨病提供新的诊断和治疗见解。

更新日期:2021-06-13
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