The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation
The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation
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DOI：
10.1073/pnas.1208916109
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发表时间：
2012-08-28
影响因子：
11.1
通讯作者：
Stevens, Molly M.
中科院分区：
文献类型：
--
作者：
Boonrungsiman, Suwimon;Gentleman, Eileen;Stevens, Molly M.
矿化是动物王国中普遍存在的过程，也是人类发展和健康的基础。功能失调或异常矿化导致各种医疗问题，因此了解这些过程对于缓解这些问题至关重要。成骨细胞通过分泌胶原性细胞外基质（ECM）产生骨的纳米复合结构，随后在其上形成磷灰石晶体。然而，尽管成骨细胞在构建骨中的必要功能和数十年的观察描述了细胞内磷酸钙，但成骨细胞在介导骨磷灰石形成中的确切作用仍然很大程度上未知。为了更好地了解细胞内和细胞外矿化之间的关系，我们结合了样品制备方法，同时保存矿物质，离子和ECM与纳米分析电子显微镜技术，以检查成骨细胞在骨形成的体外模型。我们发现磷酸钙都在成骨细胞线粒体颗粒和细胞内囊泡运输材料的ECM。此外，我们观察到含钙囊泡连接线粒体，其中也含有钙，这表明存储和运输机制。我们的观察结果进一步强调了成骨细胞内磷酸钙与其在ECM矿化中的作用之间的重要关系。这些观察结果可能对解释正常骨形成和理解病理矿化具有重要意义。
Mineralization is a ubiquitous process in the animal kingdom and is fundamental to human development and health. Dysfunctional or aberrant mineralization leads to a variety of medical problems, and so an understanding of these processes is essential to their mitigation. Osteoblasts create the nano-composite structure of bone by secreting a collagenous extracellular matrix (ECM) on which apatite crystals subsequently form. However, despite their requisite function in building bone and decades of observations describing intracellular calcium phosphate, the precise role osteoblasts play in mediating bone apatite formation remains largely unknown. To better understand the relationship between intracellular and extracellular mineralization, we combined a sample-preparation method that simultaneously preserved mineral, ions, and ECM with nano-analytical electron microscopy techniques to examine osteoblasts in an in vitro model of bone formation. We identified calcium phosphate both within osteoblast mitochondrial granules and intracellular vesicles that transported material to the ECM. Moreover, we observed calcium-containing vesicles conjoining mitochondria, which also contained calcium, suggesting a storage and transport mechanism. Our observations further highlight the important relationship between intracellular calcium phosphate in osteoblasts and their role in mineralizing the ECM. These observations may have important implications in deciphering both how normal bone forms and in understanding pathological mineralization.