Sex hormone specific effects during chondrogenic differentiation of mesenchymal stem cells

关节软骨损伤是我国人口面临的主要问题之一，给社会带来了巨大的经济损失。手术治疗的选择已经确定，但没有一种可能提供足够的结果和损伤软骨的完全再生。软骨对激素的敏感性主要被认为是绝经后出现退行性变(即骨关节炎)的原因。基于这些发现，我们假设软骨损伤后的再生也受性激素的调节。激素对软骨细胞的直接作用可能通过性激素受体、蛋白激酶依赖途径或合成代谢因子(即生长因子)的产生，而通过调节免疫反应的间接作用可能参与激素依赖的再生过程。间充质干细胞的软骨形成受性激素的调节，这在青春期生长板的生理条件下可以观察到。因此，我们假设在性激素的影响下，可以促进间充质干细胞向软骨细胞的分化，同时防止软骨肥大和骨形成的发生。这将为软骨损伤的再生提供一种新的基于性激素依赖干细胞的组织工程方法。

Injuries of articular cartilage are one of the major problems in our population with immense economical cost for the society. Surgical treatment options have been established but none may provide a sufficient outcome and a complete regeneration of injured cartilage. The hormone sensitivity of cartilage is predominately accepted for the onset of degeneration (i.e. osteoarthritis) after menopause. Based on these findings, we hypothesise that also regeneration after cartilage injury is modulated by sex hormones. Direct hormone effects on chondrocytic cells, which may be mediated via sex hormone receptors, protein kinase dependent pathways or production of anabolic factors (i.e. growth factors), and indirect effects via modulation of the immune response might be involved in the hormone dependent regeneration process. Chondrogenesis of mesenchymal stem cells is regulated by sex hormones as can be observed under physiological conditions in the growth plate during adolescence. Therefore, we hypothesise that we can improve chondrogenic differentiation of mesenchymal stem cells and simultaneously prevent the onset of cartilage hypertrophy and bone formation under the influence of sex hormones. This will lead to a new sex hormone dependent stem cell based tissue engineering approach for regeneration of cartilage injuries.