Rho GTPase protein Cdc42 is critical for postnatal cartilage development.
Rho GTPase protein Cdc42 is critical for postnatal cartilage development.
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DOI：
10.1016/j.bbrc.2016.01.111
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发表时间：
2016-02
影响因子：
3.1
通讯作者：
R. Nagahama;A. Yamada;J. Tanaka;R. Aizawa;D. Suzuki;Hidetoshi Kassai;Matsuo Yamamoto;K. Mishima;A. Aiba;K. Maki;R. Kamijo
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文献类型：
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作者：
R. Nagahama;A. Yamada;J. Tanaka;R. Aizawa;D. Suzuki;Hidetoshi Kassai;Matsuo Yamamoto;K. Mishima;A. Aiba;K. Maki;R. Kamijo
CDC42是一个小的Rho GTP酶家族成员，在体外可以调节多种细胞功能，包括肌动蛋白细胞骨架重组、细胞迁移、增殖和基因表达。然而，它在活体中的组织特异性作用在很大程度上仍不清楚，特别是在出生后的软骨发育中，因为软骨特异性的CDC42灭活小鼠在出生后几天内就会死亡。在这项研究中，我们利用他莫昔芬诱导的软骨特异性灭活的CDc42条件性基因敲除(CDc42fl/fl；Col2-CreERT)小鼠，将其与他莫昔芬诱导的II型胶原(Col2)Cre转基因小鼠杂交，建立了Cre/loxP系统，研究了CDc42在出生后软骨发育过程中的生理功能。与对照组相比，CDC42CKO组小鼠的大体形态发生改变，四肢和身体变短，体重减轻。此外，长骨生长板软骨细胞存在严重的缺陷，表现为增殖区(PZ)变短，肥大区(HZ)变宽，增殖的软骨细胞失去柱状组织，导致软骨内骨形成延迟，骨生长异常。我们的研究结果证明了CDC42在胚胎和出生后阶段对软骨发育的重要性。
Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functionsin vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific rolesin vivoremain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42fl/fl; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42fl/fl) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages.