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骨质疏松症——骨重塑与动物模型

Osteoporosis-bone remodeling and animal models.

作者信息

Bonucci Ermanno, Ballanti Paola

机构信息

Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.

Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy

出版信息

Toxicol Pathol. 2014 Aug;42(6):957-69. doi: 10.1177/0192623313512428. Epub 2013 Nov 27.

Abstract

Osteoporosis is a very common skeletal disorder characterized by reduced bone mass and altered trabecular microarchitecture that leads to bone fragility and fractures. Such disease is due to alterations of the remodeling process that occurs in the basic multicellular units that are transitory cellular complexes including an osteoclastic phase (osteoclast activation and resorption of microscopic portions of bone), a reversion phase (osteoclast replacement by so-called postosteoclastic cells), and an osteoblastic phase (osteoblastic reconstruction of the resorbed bone matrix till the initial volume is regained). Bone remodeling is regulated by a number of systemic and local factors; among the former, besides physical activity and mechanical stresses, a primary role is played by hormones such as parathyroid hormone, vitamin D metabolites, estrogens, calcitonin, and glucocorticoids; among the latter, several growth factors (macrophage colony-stimulating factor, transforming growth factor β, platelet-derived growth factor, fibroblast growth factor 1, bone morphogenetic protein, and insulin-like growth factor 1), as well as the osteoprotegerin-receptor activator of nuclear factor-κ B ligand system and the sclerostin, play a primary function. The remodeling phases can be evaluated by static and dynamic histomorphometry. Their abnormalities may lead to several osteopathies, the most common of which is osteoporosis (above all senile and postmenopausal), a rather elusive disease chiefly due to its slow development. The use of animal models in its study is emphasized.

摘要

骨质疏松症是一种非常常见的骨骼疾病,其特征是骨量减少和小梁微结构改变,进而导致骨脆性增加和骨折。这种疾病是由于在基本多细胞单位中发生的重塑过程改变所致,这些基本多细胞单位是短暂的细胞复合体,包括破骨细胞阶段(破骨细胞活化和骨微观部分的吸收)、逆转阶段(破骨细胞被所谓的破骨后细胞替代)和成骨细胞阶段(对吸收的骨基质进行成骨细胞重建,直至恢复初始体积)。骨重塑受多种全身和局部因素调节;在前者中,除了体力活动和机械应力外,甲状旁腺激素、维生素D代谢物、雌激素、降钙素和糖皮质激素等激素起主要作用;在后者中,几种生长因子(巨噬细胞集落刺激因子、转化生长因子β、血小板衍生生长因子、成纤维细胞生长因子1、骨形态发生蛋白和胰岛素样生长因子1),以及骨保护素-核因子κB配体系统受体激活剂和硬化蛋白发挥主要功能。重塑阶段可通过静态和动态组织形态计量学进行评估。它们的异常可能导致多种骨病,其中最常见的是骨质疏松症(尤其是老年性和绝经后骨质疏松症),这是一种相当隐匿的疾病,主要是因为其发展缓慢。强调了在其研究中使用动物模型。

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