Dodig M, Tadic T, Kronenberg M S, Dacic S, Liu Y H, Maxson R, Rowe D W, Lichtler A C
Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut, 06030, USA.
Dev Biol. 1999 May 15;209(2):298-307. doi: 10.1006/dbio.1999.9258.
Msx2 is believed to play a role in regulating bone development, particularly in sutures of cranial bone. In this study we investigated the effects of retroviral-mediated overexpression of Msx2 mRNA, in both sense and antisense orientations, on primary cultured chick calvarial osteoblasts. Unregulated overexpression of sense mRNA produced high levels of Msx2 protein throughout the culture period, preventing the expected fall as the cells differentiate. The continued high expression of Msx2 prevented osteoblastic differentiation and mineralization of the extracellular matrix. In contrast, expression of antisense Msx2 RNA decreased proliferation and accelerated differentiation. In other studies, we showed that the Msx2 promoter was widely expressed during the proliferative phase of mouse calvarial osteoblast cultures but was preferentially downregulated in osteoblastic nodules. These results support a model in which Msx2 prevents differentiation and stimulates proliferation of cells at the extreme ends of the osteogenic fronts of the calvariae, facilitating expansion of the skull and closure of the suture.
Msx2被认为在调节骨骼发育中发挥作用，尤其是在颅骨缝中。在本研究中，我们研究了逆转录病毒介导的Msx2 mRNA正反义方向过表达对原代培养的鸡颅盖成骨细胞的影响。正义mRNA的不受调控的过表达在整个培养期产生高水平的Msx2蛋白，阻止了细胞分化时预期的下降。Msx2的持续高表达阻止了成骨细胞分化和细胞外基质矿化。相反，反义Msx2 RNA的表达降低了增殖并加速了分化。在其他研究中，我们表明Msx2启动子在小鼠颅盖成骨细胞培养的增殖期广泛表达，但在成骨结节中优先下调。这些结果支持了一个模型，其中Msx2阻止细胞分化并刺激颅盖骨成骨前沿两端的细胞增殖，促进颅骨扩张和缝合线闭合。
