Günther Thomas, Poli Cecilia, Müller Judith M, Catala-Lehnen Philip, Schinke Thorsten, Yin Na, Vomstein Sandra, Amling Michael, Schüle Roland
Universitäts-Frauenklinik und Zentrum für Klinische Forschung, Klinikum der Universität Freiburg, Freiburg, Germany.
EMBO J. 2005 Sep 7;24(17):3049-56. doi: 10.1038/sj.emboj.7600773. Epub 2005 Aug 4.
Osteoporosis is one of the major health problems today, yet little is known about the loss of bone mass caused by reduced activity of the bone-forming osteoblasts. Here we show that mice deficient for the transcriptional cofactor four and a half LIM domains 2 (Fhl2) exhibit a dramatic decrease of bone mass in both genders. Osteopenia is caused by a reduced bone formation rate that is solely due to the diminished activity of Fhl2-deficient osteoblasts, while their number remains unchanged. The number and activity of the bone-resorbing cells, the osteoclasts, is not altered. Enforced expression of Fhl2 in differentiated osteoblasts boosts mineralization in cell culture and, importantly, enhances bone formation in transgenic animals. Fhl2 increases the transcriptional activity of runt-related transcription factor 2 (Runx2), a key regulator of osteoblast function, and both proteins interact in vitro and in vivo. In summary, we present Fhl2-deficient mice as a unique model for osteopenia due to decreased osteoblast activity. Our data offer a novel concept to fight osteoporosis by modulating the anabolic activity of osteoblasts via Fhl2.
骨质疏松症是当今主要的健康问题之一，然而对于成骨的成骨细胞活性降低所导致的骨质流失却知之甚少。在此我们表明，缺乏转录辅因子四又二分之一LIM结构域2（Fhl2）的小鼠在两性中均表现出骨量的显著下降。骨质减少是由骨形成率降低所致，而这完全归因于Fhl2缺陷型成骨细胞活性的减弱，其数量则保持不变。骨吸收细胞即破骨细胞的数量和活性并未改变。在分化的成骨细胞中强制表达Fhl2可促进细胞培养中的矿化作用，重要的是，还能增强转基因动物的骨形成。Fhl2增加了成骨细胞功能的关键调节因子—— runt相关转录因子2（Runx2）的转录活性，并且这两种蛋白在体外和体内均相互作用。总之，我们提出Fhl2缺陷型小鼠是由于成骨细胞活性降低导致骨质减少的独特模型。我们的数据提供了一个通过Fhl2调节成骨细胞的合成代谢活性来对抗骨质疏松症的新概念。
