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No binding was detected in Sirt1-/- cells. Next we tested whether Sirt1 affects the SOST promoter through modification of histone H3K9, a known Sirt1 target, using a ChIP assay. H3K9 acetylation of the SOST promoter was dramatically increased in Sirt1-/- cells in the region of maximal Sirt1 binding. Conclusions: This study demonstrates a role for Sirt1 in bone formation by repressing SOST expression via epigenetic modification of histone 3, and suggests that Sirt1 is a potential novel target for anabolic therapy for osteoporosis. Disclosures: #links# Einav Cohen-Kfir, None. 1146 Osteoblast-Specific Deletion of Neuropeptide Y1 Receptors Enhances Bone Formation.Nicola Lee, Ronaldo Enriquez, Amy Nguyen, Kharen Doyle, Amanda Sainsbury, Paul Baldock*, Herbert Herzog. Garvan Institute of Medical Research, Australia Neuropeptide Y (NPY) has been shown to play a critical role in the central regulation of bone metabolism. However, the peripheral mechanism remains unknown. In-situ hybridisation on femur sections revealed the presence of #links# the NPY, Y1 receptor mRNA in osteoblasts, consistent with a direct role for the Y1 receptor on bone cells. To investigate the role of the Y1 receptor on osteoblastic cells, we generated mice with selective deletion of the Y1 receptor in osteoblasts (Y1lox/lox, Cre/+) by crossing Y1 receptor floxed mice with mice expressing Cre specifically in osteoblasts under control of a 2.3kb fragment of the rat ��1(I)-collagen promoter. In male mice at 16 weeks of age, osteoblast-specific Y1 receptor deletion resulted in a marked increase in femoral cancellous bone volume (Y1 #links# lox/lox, Cre/+ 15.2% �� 1.4, control 11.0 �� 0.6; p<0.01), trabecular thickness (Y1lox/lox, Cre/+ 34.8 ��m �� 2.4, control 29.4 �� 1.2; p<0.05) and trabecular number (Y1lox/lox, Cre/+ 4.3 /mm �� 0.2, control 3.8 �� 0.1; p<0.05). This was the result of elevated osteoblast activity as shown by a significant increase in mineral apposition rate (Y1lox/lox, Cre/+ 1.93 ��m/day �� 0.02. control 1.64 �� 0.05; p<0.001) and bone formation rate (Y1lox/los,Cre/+ 0.52 ��m2/��m3/ day �� 0.02, control 0.41 �� 0.04; p=0.01) with no alterations in bone resorption as measured by osteoclast number and osteoclast surface area. Furthermore, osteoblastic Y1 receptor deletion also led to increased mineral apposition rate on both the endocortical (Y1lox/los,Cre/+ 1.72 ��m/day �� 0.10, control 1.08 �� 0.08; p<0.001) and the periosteal surfaces (Y1lox/los,Cre/+ 1.33 ��m/day �� 0.12, control 0.99 �� 0.07; p<0.05) resulting in significantly increased femoral diameter (Y1lox/los,Cre/+ 5.24 mm �� 0.10, control 5.00 �� 0.06; p<0.05) and a trend towards increased cortical bone strength as estimated by mean polar moment of inertia (Y1lox/los,Cre/+ 0.42 mm4 �� 0.03, control 0.36 �� 0.02; p=0.05).</p>