Abstract：
Female sex is increasingly associated with a loss of bone mass during aging and an increased risk of developing nonunion fractures. Hormonal factors and cell-intrinsic mechanisms are suggested to drive these sexual dimorphisms, although underlying molecular mechanisms are still a matter of debate. Here, we observed a decreased capacity of calvarial bone recovery in female rats and a profound sexually dimorphic osteogenic differentiation in human adult neural crest-derived stem cells (NCSCs). Next to an elevated expression of pro-osteogenic regulators, global transcriptomics revealed Lysine Demethylase 5D (KDM5D) to be highly upregulated in differentiating male NCSCs. Loss of function by siRNA or pharmacological inhibition of KDM5D significantly reduced the osteogenic differentiation capacity of male NCSCs. In summary, we demonstrated craniofacial osteogenic differentiation to be sexually dimorphic with the expression of KDM5D as a prerequisite for accelerated male osteogenic differentiation, emphasizing the analysis of sex-specific differences as a crucial parameter for treating bone defects.
摘要：
女性在衰老过程中与骨量减少和发生骨不连骨折的风险增加有关。荷尔蒙因素和细胞内在机制被认为驱动这些性二态，虽然潜在的分子机制仍然是一个争论的问题。这里,我们观察到雌性大鼠的颅骨恢复能力下降,而人类成年神经嵴来源的干细胞(NCSC)的性二形成骨分化明显.除了促成骨调节因子的表达升高之外，全球转录组学显示，赖氨酸脱甲基酶5D（KDM5D）在分化雄性NCSC中高度上调。siRNA导致的功能丧失或KDM5D的药理学抑制显著降低了雄性NCSC的成骨分化能力。总之,我们证明颅面成骨分化是性别二态的，KDM5D的表达是加速男性成骨分化的先决条件，强调性别特异性差异的分析作为治疗骨缺损的关键参数。
