BACKGROUND It is well established that adipose tissue plays a key role in energy storage and release but is also a secretory organ and a source of stem cells. Among different lineages, stem cells are able to differentiate into adipocytes and osteoblasts. As secreted proteins could regulate the balance between both lineages, we aimed at characterizing the secretome of human multipotent adipose-derived stem cell (hMADS) at an early step of commitment to adipocytes and osteoblasts. RESULTS A proteomic approach, using mono-dimensional electrophoresis and tandem mass spectrometry, allowed us to identify a total of 73 proteins at day 0 and day 3 of adipocyte and osteoblast differentiation. Analysis of identified proteins showed that 52 % corresponded to classical secreted proteins characterized by a signal peptide, that 37 % previously described in the extracellular compartment were devoid of signal peptide and that 11 % neither exhibited a signal peptide nor had been previously described extracellularly. These proteins were classified into 8 clusters according to their function. Quantitative analysis has been performed for 8 candidates: PAI-1, PEDF, BIGH3, PTX3, SPARC, ENO1, GRP78 and MMP2. Among them, PAI-1 was detected at day 0 and day 3 of osteoblast differentiation but never in adipocyte secretome. Furthermore we showed that PAI-1 mRNA was down-regulated in the bone of ovariectomized mice. CONCLUSION Given its regulation during the early events of hMADS cell differentiation and its status in ovariectomized mice, PAI-1 could play a role in the adipocyte/osteoblast balance and thus in bone diseases such as osteoporosis.

中文翻译：

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在脂肪细胞和成骨细胞分化的早期阶段表征人类间充质干细胞分泌组。

背景众所周知，脂肪组织在能量储存和释放中起关键作用，同时也是分泌器官和干细胞的来源。在不同的谱系中，干细胞能够分化为脂肪细胞和成骨细胞。由于分泌蛋白可以调节两种谱系之间的平衡，我们的目标是在脂肪细胞和成骨细胞的早期阶段表征人类多能脂肪干细胞 (hMADS) 的分泌组。结果 使用单维电泳和串联质谱的蛋白质组学方法使我们能够在脂肪细胞和成骨细胞分化的第 0 天和第 3 天鉴定总共 73 种蛋白质。对已鉴定蛋白质的分析表明，52% 对应于以信号肽为特征的经典分泌蛋白质，之前在细胞外区室中描述的 37% 没有信号肽，11% 既没有显示信号肽，也没有之前在细胞外描述过。这些蛋白质根据其功能分为8个簇。已对 8 个候选对象进行了定量分析：PAI-1、PEDF、BIGH3、PTX3、SPARC、ENO1、GRP78 和 MMP2。其中，PAI-1在成骨细胞分化的第0天和第3天检测到，但从未在脂肪细胞分泌组中检测到。此外，我们发现 PAI-1 mRNA 在去卵巢小鼠的骨骼中下调。结论 鉴于其在 hMADS 细胞分化的早期事件中的调节及其在去卵巢小鼠中的状态，PAI-1 可以在脂肪细胞/成骨细胞平衡中发挥作用，从而在骨质疏松症等骨病中发挥作用。