The Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans
The Relevance of Mouse Models for Investigating Age-Related Bone Loss in Humans
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DOI：
10.1093/gerona/glt046
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发表时间：
2013-10-01
影响因子：
5.1
通讯作者：
Jilka, Robert L.
中科院分区：
文献类型：
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作者：
Jilka, Robert L.
小鼠越来越多地被用于骨质疏松症的病理生理研究，因为它们的基因组易于操作，并且它们的骨骼与人类相似。然而，与人类骨骼不同的是，小鼠骨骼在青春期后继续缓慢生长，并且缺乏皮质骨的骨重塑。然而，像人类一样，随着年龄的增长，小鼠表现出松质骨的丧失、皮质骨的变薄和皮质孔隙度的增加。小鼠和人类的组织学证据都表明，骨重塑过程中形成的成骨细胞介导的吸收腔再填充不足是造成骨重塑的原因。小鼠早衰模型也显示骨质流失和骨骼缺陷与早期成骨细胞祖细胞衰老有关。此外，经常发生在骨质疏松参与者身上的动脉粥样硬化小鼠模型也会出现骨质流失，这表明常见的衰老疾病有共同的病理生理途径。因此，如果认识到固有的局限性，对小鼠骨骼脆性原因的了解应该适用于人类。
Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.