Ihha induces hybrid cartilage-bone cells during zebrafish jawbone regeneration
Ihha induces hybrid cartilage-bone cells during zebrafish jawbone regeneration
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DOI：
10.1242/dev.131292
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发表时间：
2016-06-15
期刊：
影响因子：
4.6
通讯作者：
Crump, J. Gage
中科院分区：
文献类型：
--
作者：
Paul, Sandeep;Schindler, Simone;Crump, J. Gage
骨的愈合通常涉及软骨中间体，然而在修复期间如何诱导和利用这种软骨还不完全清楚。通过研究成年斑马鱼下颌骨的大规模骨再生模型，我们发现软骨细胞在修复过程中对生成厚骨至关重要。在颌骨再生过程中，我们发现软骨细胞共表达与成骨细胞分化相关的基因，并产生广泛的矿化，这与面部骨骼发育过程中软骨细胞的行为形成鲜明对比。我们还确定了修复软骨细胞的可能来源，即来自骨膜的Runx 2（+）/Sp 7（-）细胞群，骨膜是一种在体内平衡期间通常只贡献成骨细胞的组织。对印度刺猬同源物a（ihha）突变体的分析表明，骨膜细胞响应于损伤而产生软骨的能力取决于Ihha在诱导中的修复特异性作用，而不是软骨细胞的增殖。因此，斑马鱼颌骨的大规模再生采用了与发育过程中所见不同的软骨分化程序，具有修复软骨细胞的骨形成潜力，这可能是由于它们衍生自骨膜中的成骨细胞。
The healing of bone often involves a cartilage intermediate, yet how such cartilage is induced and utilized during repair is not fully understood. By studying a model of large-scale bone regeneration in the lower jawof adult zebrafish, we show that chondrocytes are crucial for generating thick bone during repair. During jawbone regeneration, we find that chondrocytes co-express genes associated with osteoblast differentiation and produce extensive mineralization, which is in marked contrast to the behavior of chondrocytes during facial skeletal development. We also identify the likely source of repair chondrocytes as a population of Runx2(+)/Sp7(-) cells that emanate from the periosteum, a tissue that normally contributes only osteoblasts during homeostasis. Analysis of Indian hedgehog homolog a (ihha) mutants shows that the ability of periosteal cells to generate cartilage in response to injury depends on a repair-specific role of Ihha in the induction as opposed to the proliferation of chondrocytes. The large-scale regeneration of the zebrafish jawbone thus employs a cartilage differentiation program distinct from that seen during development, with the bone-forming potential of repair chondrocytes potentially due to their derivation from osteogenic cells in the periosteum.