Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions.
Multiple phases of chondrocyte enlargement underlie differences in skeletal proportions.
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即使是在世界自然历史博物馆的哺乳动物霍尔斯里随便走走，也会突显出骨骼比例的广泛多样性，这使我们能够区分物种，即使是在简化为钙化成分的情况下。同样，每个人都由不同长度的各种骨骼组成。对骨骼元素的延长和元素的差异性延长的最大贡献来自生长板中肥大软骨细胞的体积的急剧增加，因为它们经历终末分化。尽管这种公认的重要性，软骨细胞体积增大的机制仍然是一个谜。在这里，我们使用定量相显微镜显示，软骨细胞经历三个不同的阶段的体积增加，包括一个阶段的大量细胞肿胀，其中细胞干质量显着稀释。鉴于已知在许多细胞类型中控制体积的紧密流体调节机制，这是增加细胞大小和调节生长速率的显著机制。然而，在低密度下，在快速和缓慢伸长的生长板之间变化最大的是体积扩大的最后阶段的持续时间。此外，我们发现，这第三个阶段是通过胰岛素样生长因子依赖性机制进行局部调节。这项研究提供了一个框架，了解骨骼大小是如何调节和探索细胞如何感觉，修改，并建立一个体积设定点。
Even a casual pass through the great halls of mammals in the world’s natural history museums highlights the wide diversity of skeletal proportions that allow us to distinguish between species even when reduced to their calcified components. Similarly each individual is comprised of a variety of bones of differing lengths. The largest contribution to the lengthening of a skeletal element, and to the differential elongation of elements, comes from a dramatic increase in the volume of hypertrophic chondrocytes in the growth plate as they undergo terminal differentiation. Despite this recognized importance, the mechanisms of chondrocyte volume enlargement have remained a mystery. Here we use quantitative phase microscopy to show that chondrocytes undergo three distinct phases of volume increase, including a phase of massive cell swelling in which the cellular dry mass is significantly diluted. In light of the tight fluid regulatory mechanisms known to control volume in many cell types, this stands as a remarkable mechanism for increasing cell size and regulating growth rate. It is, however, the duration of the final phase of volume enlargement by proportional dry mass increase at low density that varies most between rapidly and slowly elongating growth plates. Moreover, we find that this third phase is locally regulated through an Insulin-like Growth Factor-dependent mechanism. This study provides a framework for understanding how skeletal size is regulated and for exploring how cells sense, modify, and establish a volume set point.
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影响因子：
2.8
作者：
Wilsman, NJ;Farnum, CE;Barreto, C
通讯作者：
Barreto, C
影响因子：
2.8
作者：
BREUR, GJ;VANENKEVORT, BA;WILSMAN, NJ
通讯作者：
WILSMAN, NJ
影响因子：
6.2
作者：
Bush, Peter G.;Pritchard, Meredith;Loqman, Mohamad Y.;Damron, Timothy A.;Hall, Andrew C.
通讯作者：
Hall, Andrew C.
影响因子：
4.1
作者：
Farnum, CE;Lee, R;Urban, JPG
通讯作者：
Urban, JPG
DOI：
10.2106/00004623-198668020-00010
发表时间：
1986-02-01
影响因子：
5.3
作者：
BUCKWALTER, JA;MOWER, D;GINSBERG, B
通讯作者：
GINSBERG, B