Hess Jochen, Hartenstein Bettina, Teurich Sibylle, Schmidt Dirk, Schorpp-Kistner Marina, Angel Peter
Deutsches Krebsforschungszentrum Heidelberg (DKFZ), Division of Signal Transduction and Growth Control (A100), Im Neuenheimer Feld 280, D-69120 Heidelberg.
J Cell Sci. 2003 Nov 15;116(Pt 22):4587-96. doi: 10.1242/jcs.00772.
Functional analysis in mice has established an absolute requirement of JunB, a member of the AP-1 transcription factor family, during early embryonic development. To investigate the role of JunB during mid and late gestation and postnatally Ubi-junB transgenic mice were used to generate two junB-/- Ubi-junB mutant lines, in which embryonic lethality was rescued but strongly reduced JunB expression in several adult tissues was observed. Mutant mice from both rescue lines were growth retarded and shared significantly reduced longitudinal bone growth. Mutant long bones were characterised by reduced numbers of growth plate chondrocytes and a severe osteoporosis. Decreased JunB levels in epiphysal growth plate chondrocytes and bone lining osteoblasts correlated with deregulated expression of Cyclin A, Cyclin D1 and p16INK4a, key regulators of cell cycle control. Furthermore, junB-/- Ubi-junB bone marrow stromal cells were unable to differentiate into bone forming osteoblasts in vitro. Our data demonstrate that JunB plays a crucial role in endochondral ossification by regulating proliferation and function of chondrocytes and osteoblasts.
小鼠体内的功能分析已证实，AP-1转录因子家族成员JunB在胚胎早期发育过程中是绝对必需的。为了研究JunB在妊娠中期、晚期及出生后的作用，利用泛素-JunB转基因小鼠构建了两个JunB基因敲除的泛素-JunB突变系，其中胚胎致死性得到挽救，但在多个成年组织中观察到JunB表达显著降低。两个挽救系的突变小鼠均生长迟缓，纵向骨生长显著减少。突变的长骨表现为生长板软骨细胞数量减少和严重的骨质疏松。骨骺生长板软骨细胞和骨内膜成骨细胞中JunB水平降低与细胞周期控制的关键调节因子细胞周期蛋白A、细胞周期蛋白D1和p16INK4a的表达失调相关。此外，JunB基因敲除的泛素-JunB骨髓基质细胞在体外无法分化为形成骨的成骨细胞。我们的数据表明，JunB通过调节软骨细胞和成骨细胞的增殖与功能，在软骨内骨化过程中发挥关键作用。
