Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, Tokyo Medical University, Tokyo, Japan.
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Biochem Biophys Res Commun. 2018 Jun 7;500(3):525-529. doi: 10.1016/j.bbrc.2018.04.032. Epub 2018 Apr 22.
Rac1 and Cdc42, Rho family low molecular weight G proteins, are intracellular signaling factors that transmit various information from outside to inside cells. Primarily, they are known to control various biological activities mediated by actin cytoskeleton reorganization, such as cell proliferation, differentiation, and apoptosis. In order to investigate the functions of Rac1 and Cdc42 in bone formation, we prepared cartilage-specific double conditional knockout mice, Rac1; Cdc42; Col2-Cre (Rac1: Cdc42 dcKO mice), which died just after birth, similar to Cdc42; Col2-Cre mice (Cdc42 cKO mice). Our findings showed that the long tubule bone in Rac1: Cdc42 dcKO mice was shorter than that in Rac1; Col2-Cre mice (Rac1 cKO mice) and Cdc42 cKO mice. Abnormal skeleton formation was also observed and disordered columnar formation in the growth plate of the Rac1: Cdc42 dcKO mice was more severe as compared to the Rac1 cKO and Cdc42 cKO mice. Together, these results suggest that Rac1 and Cdc42 have cooperating roles in regulation of bone development.
Rac1 和 Cdc42 是 Rho 家族的小分子 G 蛋白，作为细胞内信号转导因子，将各种信息从细胞外传递到细胞内。它们主要通过调控细胞骨架的重组来控制多种生物活性，如细胞增殖、分化和凋亡。为了研究 Rac1 和 Cdc42 在骨形成中的作用，我们制备了软骨特异性双条件敲除小鼠 Rac1; Cdc42; Col2-Cre（Rac1：Cdc42dcKO 小鼠），这些小鼠在出生后不久就死亡，与 Cdc42; Col2-Cre 小鼠（Cdc42 cKO 小鼠）相似。我们的研究结果表明，Rac1：Cdc42dcKO 小鼠的长管状骨比 Rac1; Col2-Cre 小鼠（Rac1 cKO 小鼠）和 Cdc42 cKO 小鼠的短。此外，还观察到异常的骨骼形成，与 Rac1 cKO 和 Cdc42 cKO 小鼠相比，Rac1：Cdc42dcKO 小鼠生长板中的柱状结构排列紊乱更为严重。综上所述，这些结果提示 Rac1 和 Cdc42 在骨发育调控中具有协同作用。
