The role of osteocytes in bone mechanotransduction
The role of osteocytes in bone mechanotransduction
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DOI：
10.1007/s00198-009-0858-5
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发表时间：
2009-06-01
影响因子：
4
通讯作者：
Klein-Nulend, J.
中科院分区：
文献类型：
--
作者：
Santos, A.;Bakker, A. D.;Klein-Nulend, J.
在日常活动中，骨骼受到各种机械载荷的影响。19世纪，Julius Wolff提出骨骼根据载荷条件调整其质量和3D结构，以优化其承载能力，这一过程是由机械应力驱动的[1]。在过去的几个世纪里，越来越多的理论和实验结果表明，骨细胞是协调这种骨质量和结构的生物力学调节的关键细胞，这种调节是通过骨重建过程完成的[2-5]骨细胞是来源于间充质前体细胞的成骨谱系的终末分化细胞。许多分子已被确定为骨细胞的重要标志，如基质细胞外磷酸糖蛋白[6]、硬化素[7]、牙本质基质蛋白-1[8]和PHEX蛋白[8]。骨细胞是成人骨骼中最丰富的细胞，在矿化的基质中不断分布。成熟的骨细胞具有特有的树突状细胞形状，突起从细胞体通过小管向不同方向辐射。这些过程通过与周围骨细胞的缝隙和贴壁连接形成细胞间网络，这些细胞排列在骨表面和骨髓内。通过这种独特的3D网络，骨细胞在解剖学上被放置在最佳位置，不仅可以感觉到施加在骨骼上的应力所驱动的变形，还可以通过信号传递给邻近的细胞[9]。十多年来，人们知道骨细胞对施加在完整骨组织上的应力非常敏感[10-16]。计算机模拟模型表明，与成骨细胞和骨衬里细胞一样，位于骨表面的机械传感器对负荷模式的变化不像位于钙化基质中的骨细胞那么敏感[3]。有趣的是，靶向消融小鼠的骨细胞干扰了骨对机械负荷的适应[16]。
Bones are subjected to a variety of mechanical loads during daily activities. In the nineteenth century, Julius Wolff proposed that bones adapt their mass and 3D structure to the loading conditions in order to optimize their loadbearing capacity, and that this process is driven by mechanical stress [1]. For the past centuries, an increasing number of theoretical and experimental results reveal that osteocytes are the pivotal cells orchestrating this biomechanical regulation of bone mass and structure, which is accomplished by the process of bone remodeling [2–5] Osteocytes are terminally differentiated cells of the osteogenic lineage that are derived from mesenchymal precursor cells. A number of molecules have been identified as important markers of osteocytes, such as matrix extracellular phosphoglycoprotein [6] sclerostin [7], dentin matrix protein-1 [8], and phex protein [8]. The osteocytes are the most abundant cells in adult bone and are constantly spaced throughout the mineralized matrix. Mature osteocytes have a characteristic dendritic cell shape, with processes radiating from the cell body through the canaliculi in different directions. These processes form an intercellular network through gap and adherent junctions with surrounding osteocytes, the cells lining the bone surface and bone marrow. Through this unique 3D network, osteocytes are anatomically placed in a prime position not only to sense deformations driven by stresses placed upon bone, but also to respond with passage of signals to the neighboring cells [9].For more than a decade now, it is known that the osteocytes are very sensitive to stress applied to intact bone tissue [10–16]. Computer simulation models have shown that mechanosensors lying at the surface of bone, as osteoblasts and bone lining cells do, would be less sensitive to changes in the loading pattern than the osteocytes, lying within the calcified matrix [3]. Interestingly, targeted ablation of osteocytes in mice disturbs the adaptation of bone to mechanical loading [16].