Aggrecan modulation of growth plate morphogenesis.
Aggrecan modulation of growth plate morphogenesis.
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生长板形态发生的Aggrecan调节。
DOI：
10.1016/j.ydbio.2009.02.024
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发表时间：
2009-05-15
影响因子：
2.7
通讯作者：
Schwartz, Nancy B.
中科院分区：
文献类型：
--
作者：
Domowicz, Miriam S.;Cortes, Mauricio;Henry, Judith G.;Schwartz, Nancy B.
关键词：
聚集蛋白聚糖遗传缺陷的鸡和小鼠胚胎表现出严重的侏儒症和过早死亡，这表明聚集蛋白聚糖在发育中起着重要作用。聚集蛋白聚糖缺陷型纳米组（nm）鸡突变体E12完全形成的生长板（GP）缺乏基质，并表现出显着改变的细胞结构，增殖能力和细胞死亡的程度。虽然成软骨细胞分化为肥大前软骨细胞（IHH表达）在E6时是正常的，但PTCH（IHH的下游效应物）的扩展骨膜表达模式表明IHH信号传导的传播改变，以及FGFR 3表达的加速下调，BrdU掺入减少和ERK磷酸化水平较高，所有这些都表明对FGF信号传导的早期影响。到E7时，IHH表达减少和COL 10A 1的过早表达预示着在E12时观察到的肥大加速。到E8，IHH和COL 10A 1的加剧的共表达导致每个元件中两个GP的延迟分离和建立。到E9，表达P-SMAD 1/5/8的细胞数量增加，表明BMP信号传导改变。这些结果表明，在聚集蛋白聚糖不存在的情况下，IHH、FGF和BMP信号传导途径从GP形成的一开始就发生了改变，从而诱导过早的肥大软骨细胞成熟，导致nanomelic长骨生长障碍。
Chick and mouse embryos with heritable deficiencies of aggrecan exhibit severe dwarfism and premature death, demonstrating the essential involvement of aggrecan in development. The aggrecan-deficient nanomelic (nm) chick mutant E12 fully formed growth plate (GP) is devoid of matrix and exhibits markedly altered cytoarchitecture, proliferative capacity, and degree of cell death. While differentiation of chondroblasts to pre-hypertrophic chondrocytes (IHH expression) is normal up to E6, the extended periosteum expression pattern of PTCH (a downstream effector of IHH) indicates altered propagation of IHH signaling, as well as accelerated down-regulation of FGFR3 expression, decreased BrdU incorporation and higher levels of ERK phosphorylation, all indicating early effects on FGF signaling. By E7 reduced IHH expression and premature expression of COL10A1 foreshadow the acceleration of hypertrophy observed at E12. By E8, exacerbated co-expression of IHH and COL10A1 lead to delayed separation and establishment of the two GPs in each element. By E9, increased numbers of cells express P-SMAD1/5/8, indicating altered BMP signaling. These results indicate that the IHH, FGF and BMP signaling pathways are altered from the very beginning of GP formation in the absence of aggrecan, thereby inducing premature hypertrophic chondrocyte maturation, leading to the nanomelic long bone growth disorder.
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DOI：
10.1083/jcb.126.6.1611
发表时间：
1994-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Amizuka N;Warshawsky H;Henderson JE;Goltzman D;Karaplis AC
通讯作者：
Karaplis AC
影响因子：
7.2
作者：
Chen, M;Wang, J
通讯作者：
Wang, J
影响因子：
11.8
作者：
de Frutos, Cristina A.;Vega, Sonia;Nieto, M. Angela
通讯作者：
Nieto, M. Angela
影响因子：
9.8
作者：
Gleghorn, L;Ramesar, R;Wallis, G
通讯作者：
Wallis, G
影响因子：
4
作者：
Garcia, Sofia;Lopez, Edith;Lopez-Colome, Ana Maria
通讯作者：
Lopez-Colome, Ana Maria