Characterization of human mesenchymal stem cell secretome at early steps of adipocyte and osteoblast differentiation

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.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.Adipose tissue is no longer considered as a mere energy reservoir but it plays also an endocrine role, releasing a panoply of secreted molecules, i.e. adipokines such as leptin, adiponectin, plasminogen activator inhibitor 1 (PAI-1), vaspin and tumor necrosis factor α (TNFα) [1,2]. Furthermore, adipose tissue is a source of stem cells, representing a promising tool for pharmacological studies and clinical applications [3]. A balanced development of adipose tissue is of crucial importance to ensure some of the most important physiological functions, including reproduction, haemostasis, angiogenesis, blood pressure and immune function [1,4]. Alterations of fat cell number and size are present in lipodystrophy and obesity that are associated to type 2 diabetes [5]. Another condition altering fat cell formation is osteoporosis, where an imbalance betwe