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cxpliquee, au moins en partie, par une diminution de la concentration sanguine en leptine et des perturbations dans la voie de signalisation Wnt dans les CSM.

3.3 Abstract

CD36 is expressed by bone-forming osteoblasts but its contribution to bonę metabolism is still poorly documented. We have recently reported that Cd36-nuli mice show Iow bonę mass associated with reduced bonę formation. Here, we further characterize the systemie and local factors involved in bonę metabolism and the in vitro cellular behavior of mesenchymal stromal cells (MSCs) lacking Cd36. Cd36-null mice show lipodystrophy associated with Iow plasma levels of leptin (lep) and a reduced leptin/adiponectin ratio. Lep gene expression by Cd36-nuli MSCs was reduced by 60% compared to wild type (WT) MSCs. Lower proliferation ratę, reduced celi survival and inereased apoptosis level were evidence in Cd36-nuli MSCs cultured for 21 days. Cd36-nuli MSCs also show over expression of Ppary involved in celi growth, regulation of apoptosis and celi cycle. Moreover, genetic expression of Gli-l and forkhead-01 (Foxol) was also inereased in Cd36-nuli MSCs. Gene expression of the chondrogenic transcription factor Sox9 was inereased and marker of maturę chondrocyte Col-IIa was unchanged in Cd36-nuli MSCs, in accordance with the absence of differences in growth piąte morphology between both genotypes. The study of Wnt signaling pathway reveals normal response in WT and Cd36-nuli MSCs, as evidenced by similar Wnt3a-induced upregulation of the target gene Axin2. However, gene expression of Wnt3a by Cd36-nuli MSCs was reduced by 40% and Wnt5a by 50% when compared to WT cells. There was no difference in gene expression of Lrp5/6 and Rspo2. Moreover, gene expression of Sost and Dkkl, two antagonists of the Wnt pathway were inereased by 1.8 and 3.4-fold, respectively. Our results suggest that the Iow bonę mass phenotype of Cd36-nuli mice may be