Toward an understanding of the short bone phenotype associated with multiple osteochondromas.
Toward an understanding of the short bone phenotype associated with multiple osteochondromas.
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DOI：
10.1002/jor.22280
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发表时间：
2013-04
影响因子：
2.8
通讯作者：
Capecchi, Mario R.
中科院分区：
文献类型：
--
作者：
Jones, Kevin B.;Datar, Manasi;Ravichandran, Sandhya;Jin, Huifeng;Jurrus, Elizabeth;Whitaker, Ross;Capecchi, Mario R.
患有多发性骨软骨瘤（MO）的个体表现出长骨缩短。 Ext1 或 Ext2 单倍体不足无法重现小鼠的表型。 Ext1 杂合性的丧失可能会导致骨软骨瘤纵向生长的缩短或骺信号传导的普遍紊乱而导致缩短。我们在小鼠遗传模型中骨骼生长过程中的不同时间点诱导骨软骨瘤发生，然后使用显微 CT 和基于点分布的形状分析在 12 周时分析股骨和胫骨。比较骨骼长度和体积。作为表型扩大的衡量标准，干骺端体积与正常值的偏差与长度偏差相关。患有骨软骨瘤的小鼠的股骨和胫骨比对照组更短，当骨软骨瘤发生在骨骼生长过程中较早诱导时更一致。体积干骺端增宽与纵向缩短无关，尽管一些最严重的缩短发生在具有大量骨软骨瘤的骨骼中。 Ext1 杂合性的丧失足以驱动 MO 小鼠模型中的骨缩短，但缩短与骨软骨瘤体积生长无关。虽然偷窃现象在个别病例中似乎很明显，但其他一些机制也必须能够导致短骨表型，而与骨软骨瘤的形成无关。缺乏功能性硫酸乙酰肝素的软骨细胞克隆必须总体上削弱骨骺信号传导，而不是局部窃取生长潜力。
Individuals with multiple osteochondromas (MO) demonstrate shortened long bones. Ext1 or Ext2 haploinsufficiency cannot recapitulate the phenotype in mice. Loss of heterozygosity for Ext1 may induce shortening by steal of longitudinal growth into osteochondromas or by a general derangement of physeal signaling. We induced osteochondromagenesis at different time points during skeletal growth in a mouse genetic model, then analyzed femora and tibiae at 12 weeks using micro-CT and a point-distribution-based shape analysis. Bone lengths and volumes were compared. Metaphyseal volume deviations from normal, as a measure of phenotypic widening, were correlated with length deviations. Mice with osteochondromas had shorter femora and tibiae than controls, more consistently when osteochondromagenesis was induced earlier during skeletal growth. Volumetric metaphyseal widening did not correlate with longitudinal shortening, although some of the most severe shortening was in bone with abundant osteochondromas. Loss of heterozygosity for Ext1 was sufficient to drive bone shortening in a mouse model of MO, but shortening did not correlate with osteochondroma volumetric growth. While a steal phenomenon seems apparent in individual cases, some other mechanism must also be capable of contributing to the short bone phenotype, independent of osteochondroma formation. Clones of chondrocytes lacking functional heparan sulfate must blunt physeal signaling generally, rather than stealing growth potential focally.
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DOI：
10.1073/pnas.0910875107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Jones, Kevin B.;Piombo, Virginia;Sheffield, Val C.
通讯作者：
Sheffield, Val C.
影响因子：
4.6
作者：
Stickens, D;Zak, BM;Werb, Z
通讯作者：
Werb, Z
影响因子：
4.8
作者：
Busse, Marta;Feta, Almir;Kusche-Gullberg, Marion
通讯作者：
Kusche-Gullberg, Marion
影响因子：
2.7
作者：
GLORFELD, LW
通讯作者：
GLORFELD, LW
影响因子：
4.5
作者：
Clément A;Wiweger M;von der Hardt S;Rusch MA;Selleck SB;Chien CB;Roehl HH
通讯作者：
Roehl HH