Zhang J, Zhu J, Valverde P, Li L, Pageau S, Tu Q, Nishimura R, Yoneda T, Yang P, Zheng W, Ma W, Chen J
Division of Oral Biology, Department of General Dentistry, Tufts University School of Dental Medicine, One Kneeland Street, Boston, MA 02111, USA.
J Dent Res. 2008 Jan;87(1):45-50. doi: 10.1177/154405910808700107.
Dlx5 plays an important role in the embryonic development of mineralized tissues. We hypothesized that Dlx5 also functions in regulating post-natal bone formation in mice. To prove this hypothesis, we infected 5-day-old bone sialoprotein (BSP)/avian retroviral receptor gene (TVA) transgenic mice with replication-competent retroviral vectors expressing wild-type Dlx5 (RCAS-Dlx5WT) and mutated Dlx5 at arginine (R) 31 of its homeodomain (RCAS-Dlx5RH). Immunohistochemistry indicated that RCAS-Dlx5WT increased BSP and osteopontin (OPN) expression, whereas it decreased that of osteocalcin (OC). RCAS-Dlx5RH mediated opposite effects. Semi-quantitative RT-PCR confirmed these results. Ex vivo overexpression of RCAS-Dlx5WT in BSP/TVA calvarial cells promoted, whereas that of RCAS-Dlx5RH inhibited, mineralized nodule formation as compared with that in control cells. Our results suggest that Dlx5 promotes expression of early markers of osteogenic differentiation and increases mineralization post-natally.
Dlx5在矿化组织的胚胎发育中起重要作用。我们推测Dlx5在调节小鼠出生后骨形成中也发挥作用。为了验证这一假设，我们用表达野生型Dlx5（RCAS-Dlx5WT）和其同源结构域第31位精氨酸（R）突变的Dlx5（RCAS-Dlx5RH）的具有复制能力的逆转录病毒载体感染5日龄骨唾液蛋白（BSP）/禽逆转录病毒受体基因（TVA）转基因小鼠。免疫组织化学表明，RCAS-Dlx5WT增加了BSP和骨桥蛋白（OPN）的表达，而降低了骨钙素（OC）的表达。RCAS-Dlx5RH介导相反的作用。半定量RT-PCR证实了这些结果。与对照细胞相比，在BSP/TVA颅骨细胞中RCAS-Dlx5WT的体外过表达促进了矿化结节的形成，而RCAS-Dlx5RH的过表达则抑制了矿化结节的形成。我们的结果表明，Dlx5促进成骨分化早期标志物的表达，并在出生后增加矿化。
