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development and regulate injury-induced angiogenesis in adult tissue (Renault et al., 2010). It was recently reported that SHH signaling proteins, including Gli-I, are upregulated in Cd36-nuli bonę marrow angiogenic cells suggesting implication of this pathway in CD36’s regulation of angiogenesis (Wang et al, 2013). Our previous study demonstrates Runx2 downregulation in Cd36-nuli mice (Kevorkova et al., 2013). Interestingly, Cbfal/Runx2 deficient mice show reduced bonę angiogenesis, diminished blood vessel invasion and lack of VEGF and VEGF receptor expression in hypertrophic chondrocytes (Zelzer et al., 2001). Moreover, inadeąuate bonę vascularity is associated with decreased bonę formation and bonę mass (Portal-Nunez et al., 2012). Additional studies are reąuired to evaluate the angiogenesis status in Cd36-nuli bonę.

Our data show upregulation of Foxol in Cd36-nuli MSCs. This finding agrees with reports that Foxol overexpression in MC3T3-E1 cells reduces proliferation (Siqueira et al., 2011). Moreover, FOX01 was found to contribute to apoptosis. In numerous celi types, activation of the FOXO family leads to apoptosis, particularly when its expression or activation is prolonged. FOX01 induces the expression of a large number of proapoptotic mediators such as TNF-a, FAS ligand, TRAIL and caspases (Alikami et al, 2005 ; Giley et al., 2003). Diabetic mice show increased chondrocyte apoptosis through enhanced production of TNF-a and FOX01 activation (Kayal et al., 2010). Increased number of apoptotic cells leads to secondary necrosis, which in tum releases cytotoxic factors that alter celi behavior and functions (Elliott et Ravichandran, 2010). Thus, we cannot exclude increased cytotoxin accumulation in prolonged culture of Cd36-nuli MSCs which results in formation of apoptotic and necrotic cells. In addition, CD36 is implicated in celi adhesion (Oquendo et al, 1989), consequently the increased necrotic celi number may be related to impaired MSCs adherence. Some studies State a vital relationship between FOXOs and Ccns; these factors are believed to stabilize the G1 and G2/M celi cycle checkpoints by inhibiting CcnD and CcnA (for a review, see (Ho et al., 2008)). As a result, apoptosis