Histological evidence of the altered distribution of osteocytes and bone matrix synthesis in klotho-deficient mice
Histological evidence of the altered distribution of osteocytes and bone matrix synthesis in klotho-deficient mice
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DOI：
10.1679/aohc.68.371
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发表时间：
2005-12-01
影响因子：
--
通讯作者：
Maeda, T
中科院分区：
文献类型：
--
作者：
Suzuki, H;Amizuka, N;Maeda, T
klotho 基因缺失的纯合小鼠是公认的衰老模型，因为它们模仿人类衰老的某些方面，例如衰老。骨质疏松症。诱导衰老可能影响细胞功能并改变细胞外基质的组织学特性。本研究检查了 klotho 缺陷小鼠骨细胞和周围骨基质的组织学和超微结构特征。正如预期的那样，成骨细胞呈扁平形状，对碱性磷酸酶的免疫反应性较弱，骨基质中含有许多空的骨细胞腔隙。正常和空陷窝壁的骨桥蛋白和牙本质基质蛋白-1 均呈强烈免疫阳性，但骨钙素和 I 型胶原蛋白的免疫反应性不一致。毫不奇怪，在 klotho 缺陷小鼠的许多成骨细胞、骨细胞和骨髓细胞中发现了 TUNEL 阳性，表明细胞凋亡。在透射电子显微镜中，在成骨细胞周围和骨细胞腔隙中可以识别出含有非胶原有机材料的无定形基质。骨表面的一些成骨细胞在与其跨高尔基体网络相关的液泡中呈现这些无定形材料，这表明在克洛索缺乏的条件下，它们合成并分泌非胶原结构。一些骨细胞表现出固缩或退化特征。因此，我们的研究结果提供了组织学证据，表明除了骨细胞加速老化之外，klotho基因缺失还影响骨细胞的空间分布和骨基质蛋白的合成。
Mice homozygous for klotho gene deletion are well established aging models as they mimic certain aspects of human senescence e.g. osteoporosis. Induced senescence may affect cellular functions and alter the histological properties of the extracellular matrices. The present study examined the histological and ultrastructural features of osteocytes and the surrounding bone matrix in klotho-deficient mice. As expected, osteoblasts showed a flattened shape with a weak immunoreactivity for alkaline phosphatase, and the bone matrix contained many empty osteocytic lacunae. The walls of both normal and empty lacunae were intensely immunopositive for osteopontin and dentin matrix protein-1, but featured an inconsistent immunoreactivity for osteocalcin and type I collagen. Not surprisingly, TUNEL-positivity, indicative of apoptosis, was found in many osteoblasts, osteocytes, and bone marrow cells of the klotho-deficient mice. In transmission electron microscopy, an amorphous matrix containing non-collagenous organic materials was recognizable around osteoblasts and in the osteocytic lacunae. Some osteoblasts on the bone surface featured these amorphous materials in vacuoles associated with their trans-Golgi network, indicating that, under klotho-deficient conditions, they synthesize and secrete the non-collagenous structures. Some osteocytes displayed pyknosis or degenerative traits. Thus, our findings provide histological evidence that klotho gene deletion influences the spatial distribution of osteocytes and the synthesis of bone matrix proteins in addition to the accelerated aging of bone cells.