Two populations of endochondral osteoblasts with differential sensitivity to Hedgehog signalling
Two populations of endochondral osteoblasts with differential sensitivity to Hedgehog signalling
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DOI：
10.1242/dev.042150
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发表时间：
2009-12-01
期刊：
影响因子：
4.6
通讯作者：
Schulte-Merker, Stefan
中科院分区：
文献类型：
--
作者：
Hammond, Christina Lindsey;Schulte-Merker, Stefan
Hedgehog（Hh）信号传导与成骨细胞和破骨细胞的发育有关，成骨细胞和破骨细胞的平衡活性对于适当的骨形成至关重要。由于Hh通路中的许多小鼠突变体是胚胎致死的，因此关于Hh信号传导对骨生成的确切影响的问题仍然存在。使用斑马鱼，我们发现，有两个群体的endochondrium成骨细胞与差异敏感性Hh信号。一种是在软骨结构外形成的，需要低水平的Hh信号传导，并且不能在印度刺猬突变体中分化。另一种来源于软骨细胞，需要更高水平的Hh信号才能形成。后一种人群在Hh信号传导增加的突变体中显着提前发育，导致过早的软骨内骨化，并且在印度刺猬突变体中也未能分化，导致严重延迟的软骨内骨化。此外，我们证明，破骨细胞的第一次活动的时间呈正相关的Hh水平在endochondrium和真皮骨。
Hedgehog (Hh) signalling has been implicated in the development of osteoblasts and osteoclasts whose balanced activities are critical for proper bone formation. As many mouse mutants in the Hh pathway are embryonic lethal, questions on the exact effects of Hh signalling on osteogenesis remain. Using zebrafish, we show that there are two populations of endochondral osteoblasts with differential sensitivity to Hh signalling. One, formed outside the cartilage structure, requires low levels of Hh signalling and fails to differentiate in Indian hedgehog mutants. The other derives from chondrocytes and requires higher levels of Hh signalling to form. This latter population develops significantly earlier in mutants with increased Hh signalling, leading to premature endochondral ossification, and also fails to differentiate in Indian hedgehog mutants, resulting in severely delayed endochondral ossification. Additionally, we demonstrate that the timing of first osteoclast activity positively correlates to Hh levels in both endochondral and dermal bone.