Sox9 Expression during Fracture Repair
Sox9 Expression during Fracture Repair
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DOI：
10.1159/000322557
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发表时间：
2011-01
影响因子：
2.7
通讯作者：
Y. Shintaku;Takashi Murakami;T. Yanagita;N. Kawanabe;T. Fukunaga;Kiyomi Matsuzaki;S. Uematsu;Yasuhiro Yoshida;H. Kamioka;T. Takano-Yamamoto;K. Takada;T. Yamashiro
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文献类型：
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作者：
Y. Shintaku;Takashi Murakami;T. Yanagita;N. Kawanabe;T. Fukunaga;Kiyomi Matsuzaki;S. Uematsu;Yasuhiro Yoshida;H. Kamioka;T. Takano-Yamamoto;K. Takada;T. Yamashiro
参与骨发育的分子和细胞机制提供了对骨再生性质的深入了解。Sox 9是软骨形成的关键转录因子，并且在胚胎骨发育期间也在骨软骨祖细胞中表达。然而，还没有确定Sox 9表达细胞是否出现在骨折修复过程中，而不是在软骨愈伤组织中。另一方面，骨发育和修复之间的区别在于骨折节段的运动与骨软骨形成前体在骨形成或软骨形成之间的后续命运决定相关，但其潜在机制仍有待阐明。我们在此评估Sox9表达细胞是否出现在体内骨折愈合的初始阶段的骨再生过程中。我们还研究了Sox 9诱导和机械应力之间的关联以及Runx 1表达的作用。结果，在骨膜骨痂中检测到Sox 9和Runx 1表达细胞以及Runx 2表达。它们的表达水平在其骨化过程中显著下调，如在胚胎骨发育中所观察到的。应用周期性张力分离和培养的基质细胞导致Sox 9 mRNA表达的上调和维持在体外。这些结果表明，在早期骨骼发育，Sox9和Runx1表达的前体细胞首先出现在骨膜骨痂作为早期骨折修复反应。我们的研究结果还表明，机械环境调节Sox9的表达水平在骨软骨形成的前体，从而影响他们的命运决定之间的成骨和软骨形成的谱系承诺。
The molecular and cellular mechanisms involved in bone development provide an insight into the nature of bone regeneration. Sox9 is a key transcription factor for chondrogenesis and is also expressed in osteochondroprogenitors during embryonic bone development. However, it has not been determined whether Sox9-expressing cells appear during fracture repair other than in the cartilaginous callus. On the other hand, the difference between bone development and repair is that the motion of the fractured segments is associated with the subsequent fate decision of osteochondrogenic precursors between osteogenesis or chondrogenesis, but the underlying mechanism of this still has to be elucidated. We herein evaluate whether Sox9-expressing cells appear during osseous regeneration in the initial stages of fracture healing in vivo. We also investigated the association between Sox9 induction and mechanical stress and the role of Runx1 expression. As a result, Sox9- and Runx1-expressing cells were detected in the periosteal callus together with Runx2 expression. Their expression levels were significantly downregulated during its ossification, as observed in embryonic bone development. The application of cyclic tension to isolated and cultured stromal cells resulted in the upregulation and maintenance of Sox9 mRNA expression in vitro. These results showed that as in early skeletal development, Sox9- and Runx1-expressing precursor cells first appear in the periosteal callus as an early fracture repair response. Our findings also suggested that the mechanical environment modulates Sox9 expression levels in osteochondrogenic precursors and consequently influences their fate decision between osteogenic and chondrogenic lineage commitment.