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shown in Fig. 3.2E, growth piąte morphology and thickness was comparable between Cd36-nuli and WT mice; moreover, our previous results report similar femur and tibia length in Cd36-nuli and WT mice at 1-3 months of age (Kevorkova et al., 2013).

3.6.2 Celi proliferation and survival

Since our previous results indicated reduced bonę formation ratę and impaired functions of Cd36-nu\\ MSCs (Kevorkova et al., 2013), we further characterized the in vitro behavior of MSCs lacking Cd36. There was no difference in number of total bonę marrow MSCs per mouse at seeding (Fig. 3.3A). As shown in Fig. 3B, at day 7 post seeding the rates of proliferation and apoptosis of Cd36-mi\\ and WT MSCs were similar; however at day 14 and 21 Cd36-nuli MSCs showed reduced celi number, accompanied by a higher percentage of apoptotic cells relatively to WT cells. Indeed, apoptosis of adherent cells was increased almost 3-fold in Cd36-nuli MSCs when compared to WT MSCs at day 14 (5.3%±1.3% vs 1.6%±0.4%) and over 3-fold at day 21 (7.2%±1.0% vs 2.9%±0.5%). Moreover, the level of apoptotic and necrotic cells in supematant was nearly 3 times greater at day 21 post seeding in nuli MSCs (27.3%±0.5%) compared to WT cells (11.5%±2.3%) (Fig. 3.3C). Gene expression of cyclin (Cen) A2 and DI was significantly higher in Cd36-null MSCs under basal conditions, suggesting deregulation of celi cycle (Fig. 3.3D). However, the proportion of cells in the different stages of celi cycle was however comparable between both genotypes (Tab. 3.2). We therefore explored how the nuli cells behaved in the presence of known CD36 ligands.

3.6.3 Effects of CD36 ligands

Given that TSP-1 and hexarelin are two major ligands for CD36 (Park, 2014), we investigated their effect on celi behavior in vitro. In order to verify the effect of these