Bone Regenerates via Dedifferentiation of Osteoblasts in the Zebrafish Fin
Bone Regenerates via Dedifferentiation of Osteoblasts in the Zebrafish Fin
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DOI：
10.1016/j.devcel.2011.04.014
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发表时间：
2011-05-17
影响因子：
11.8
通讯作者：
Weidinger, Gilbert
中科院分区：
文献类型：
--
作者：
Knopf, Franziska;Hammond, Christina;Weidinger, Gilbert
虽然哺乳动物修复骨缺陷的能力有限，但斑马鱼可以完全再生它们鳍的截骨结构。鳍的再生依赖于胚泡的形成，胚泡是在截肢平面聚集的前体细胞池。目前尚不清楚胚泡来自哪些细胞，是否由成熟细胞去分化形成，以及胚泡细胞是否具有多能性。我们发现成熟的成骨细胞去分化，形成胚泡的一部分。成骨细胞下调中晚期骨分化标志物的表达，并诱导骨祖细胞表达基因。去分化的成骨细胞以成纤维细胞生长因子依赖的方式增殖，并迁移形成胚泡的一部分。基因命运图谱显示，成骨细胞只在再生过程中产生成骨细胞，这表明去分化与获得多能性无关。因此，骨可以通过去分化从成熟的成骨细胞再生，这一发现对人类骨修复具有潜在的意义。
While mammals have a limited capacity to repair bone defects, zebrafish can completely regenerate amputated bony structures of their fins. Fin regeneration is dependent on formation of a blastema, a progenitor cell pool accumulating at the amputation plane. It is unclear which cells the blastema is derived from, whether it forms by dedifferentiation of mature cells, and whether blastema cells are multipotent. We show that mature osteoblasts dedifferentiate and form part of the blastema. Osteoblasts downregulate expression of intermediate and late bone differentiation markers and induce genes expressed by bone progenitors. Dedifferentiated osteoblasts proliferate in a FGF-dependent manner and migrate to form part of the blastema. Genetic fate mapping shows that osteoblasts only give rise to osteoblasts in the regenerate, indicating that dedifferentiation is not associated with the attainment of multipotency. Thus, bone can regenerate from mature osteoblasts via dedifferentiation, a finding with potential implications for human bone repair.