3513659561

107

genotypes. However, gene expression of Wnt3a and WntS ligands in Cd36-nuli MSCs were reduced by 40% and 50%, respectively, compared to WT cells (Fig. 3.6B). Moreover, gene expression of Sost and Dkkl_t two antagonists of the Wnt pathway, were increased by 1.8 and 3.4-fold, respectively (Fig. 3.6C). Basal expression level of Axin2 was identical in WT and Cd36-nuli MSCs, but gene expression of Lefl in unstimulated cells was lower in CD36 deficient cultures (Fig. 3.7A, B). Because Wnt3a is classically used to induce Wnt target-genes, we tested whether lack of Cd36 impaired the Wnt canonical pathway; Wnt3a treatment generated a similar genetic upregulation of transcriptional gene target Axin2 in WT and Cd36-nuli MSCs (Fig. 3.7B).

3.7 Discussion

We recently reported impaired bonę formation in the long bonę and vertebrae of Cd36-rm\\ mice (Kevorkova et al., 2013); the present study further investigated the role of CD36 in the physiology of bonę marrow-derived MSCs. Our results indicate that, concomitantly to Iow leptinemia, CD36 deficiency causes a drastic increase in number of apoptotic and necrotic MSCs, as well as significant loss of viability in vitro. Moreover, the expression of Ppary, a target-gene of CD36, as well as that of Wnt signaling ligands was affected by CD36 deficiency.

Numerous systemie and local factors influence bonę homeostasis, such as the peptidic hormone leptin known to regulate bonę mass via central and peripheral mechanisms. In vitro> leptin stimulates osteoblast proliferation and differentiation while inhibiting osteoclastogenesis. In vivo, peripheral leptin administration inereases bonę mass and reduces bonę fragility (Comish et al., 2002; Turner et al._y 2013), and inereases periosteal bonę formation and commitment of MSCs towards osteoblasts (Thomas et al._y 1999). Circulating leptin is mainly secreted by adipose tissue (Zhang et al.y 1994)