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aforementioned studies stating the cells and tissue dysfunctions induced by lack of CD36 (Eto et al._y 2003; Vroegrijk et al., 2013; Won et al., 2008).

As Cd36-nuli cells show impaired basal proliferation and higher apoptosis, we investigated their response to known CD36-specific ligands. Hexarelin is a synthetic peptide of the growth hormone-releasing peptides family known to exert cardiovascular effects through CD36 binding (Bodart et al., 2002). TSP-1 is an antiangiogenic factor reported to inhibit tubę formation by bonę marrow-derived angiogenic cells in vitro via a CD36-dependent mechanism (Wang et al., 2013).Our data show that exposure to hexarelin or TSP-1 enhances MC3T3-E1 preosteoblast and WT but not Cd36-nuli MSCs proliferation. We can hypothesize that CD36 is not only implicated in balance between proliferation and apoptosis under basal conditions, but also in ligand-induced proliferative responses of bonę marrow derived MSCs. To conclusively support a specific role for CD36 in celi proliferation, the response of Cd36-nuli MSCs to other growth factors independent of CD36 such as FGF or PDGF could be investigated.

A common downstream factor involved in hexarelin and TSP-1 binding to CD36 is PPARy (Demers et al., 2008; Zhang et al., 2014); we therefore verified whether its basal expression was altered by Cd36 deficiency. Since the transcription factor PPARy regulates commitment of MSCs towards adipogenesis (Fakhry et al., 2013), over-expression of Ppary in Cd36-nuli MSCs should lead to increased adiposity, which is not the case given that fat reserve is reduced in the Cd36-nuli mice. PPARy is also known to be involved in celi growth and its activation promotes apoptosis and celi cycle arrest (Elrod et Sun, 2008). Thus, increased cells apoptosis and lower proliferation leading to Iow bonę mass and decreased adipogenesis may be related to over expression of Ppary in Cd36-nuli MSCs. We also observed increased expression of transcriptional factor Gli-I in Cd36-nu\\ MSCs. GLI-I induces the expression of downstream target molecules in the SHH pathway that govem embryonic vascular