more in the LVB than in the CVB in response to Scl-Ab treatment. However, MS/BS and BFR/BS increased more in the CVB than in the LVB in response to Scl-Ab treatment. Conclusion: Our findings indicate that the inhibition of sclerostin via Scl-Ab increased bone formation, bone mass, and trabecular width and decreased bone resorption in both the high and low bone turnover sites. Bone mass and trabecular width increased more in high bone turnover site than in low bone turnover site, while bone formation increased more in low bone turnover site than in high bone turnover site in response to Scl-Ab treatment. The different magnitude of the increase in bone mass between the high and low bone turnover sites may stem from stronger anti-resorptive effects of Scl-Ab in the high bone turnover site than in the low turnover site. doi:10.1016/j.bone.2008.07.030 OR11 Sclerostin inhibits bone growth via antagonizing Wnt/beta-catenin signaling, and via stimulating cell death Chuwen Lin, Lin He Bio-X Center, Shanghai Jiao-tong University Medical School, Shanghai, China Objective: Sclerostin, encoded by gene Sost, has emerged as a potent negative regulator of bone formation, and also a promising therapeutic target for treatment of osteoporosis. However, the mechanism underlying its function remains unclear in vivo. Sclerostin is originally characterized as an antagonist of BMP signaling and it binds BMPs, but it has also been shown to bind LRP5/6 in vitro. This study reveals the mechanism of Sclerostin's function. Methods: Sost null mice were generated by replacing the coding sequence of Sost with a LacZ-Neo cassette. Bone densitometer was utilized to examine the bone mass of Sost null mice. Micro CT, radiograph, calcein labeling and subsequent bone histomorphometric analysis were used to evaluate the bone architecture, bone volume, bone formation rate, and osteoblast number of Sost null mice. E14.5 and E16.5 tibias were subjected to paraffin section and H.E staining. Alcian blue and alizarin red staining of P1 skeleton were performed to examine the bone development. 8-week tibia was decalcified and the paraffin section was subjected to TRAP staining. Western blot using protein and extracted from 8-week mouse femur was performed to examine the activity of Wnt/beta-catenin signaling, the BMP signaling, and apoptosis. Results: The bone mass of Sost null mice are strikingly elevated compared with those of wildtype (WT) at ages from 4 weeks to 24 weeks. The bone volume, bone formation rate, and osteoblast number of Sost null mice were also highly increased. H.E staining of E14.5 and E16.5 tibia sections together with double staining of P1 skeleton revealed no defect in bone development. TRAP staining shows no change in the activity of bone resorption, indicating that the high bone mass defect in Sost null mice is due to alteration in bone formation. Furthermore, the Wnt/beta-catenin signaling was enhanced in Sost-deficient bone indicated by increased expression of the target genes and nuclear localization of beta-catenin, while the BMP signaling activity didn't change as shown by level of phosphorylated SMAD1/5/8. Interestingly, we also observed that apoptosis of bone cells is decreased in Sost-deficient bone. Conclusion: Thus, we demonstrate that sclerostin inhibits bone formation via antagonizing Wnt/beta-catenin signaling specifically and via stimulating bone cell apoptosis in addition. doi:10.1016/j.bone.2008.07.031 OR12 Potential roles of growth factor PDGF in the mesenchymal progenitor cell infiltration and bony repair at the injured growth plate Rosa Chung 1 , Bruce Foster 2 , Cory Xian 3 1 University of Adelaide, Australia 2 Women's and Children's Hospital, Adelaide, Australia 3 University of South Australia, Adelaide, Australia Injured growth plate is often repaired undesirably by bony tissue resulting in bone growth defects in children. Our previous studies in young rats with injured growth plate have demonstrated that, prior to the bony repair within the injury site, there are an initial inflammatory response and a subsequent influx of mesench- ymal cells including progenitor cells with the capacity to differentiate into chondrocytes and/or bone cells. In addition, during the inflammatory and mesenchymal responses, expression of the platelet-derived growth factor (PDGF-B) was shown to be up-regulated. Since PDGF-B is known to be an important growth, chemotactic, and survival factor for mesenchymal progenitor cells and for skeletal tissue growth and repair, this study examined potential roles of PDGF-B in the bony repair of injured growth plate in young rats which received 1 week of once-daily injections of vehicle or PDGF receptor inhibitor Imatinib®. Mesenchymal cell infiltration, chondrogenic and osteogenic responses and bony repair within the injury site were analysed histologically. By day 4, less mesenchymal infiltrate was evident in Imatinib®-treated rats compared to vehicle control. Consistently, in vitro cell migration assay demonstrated a chemotactic role of PDGF-B in rat bone marrow mesenchymal cells and the inhibitory effect of Imatinib®. By day 10 after injury, Imatinib®-treated rats had a significantly lower level of cartilaginous repair tissue (p®-treated rats had a lower number of osteoclasts in the remodelling repair site and consistently there was a lower expression level of osteoclastogenic and angiogenic growth factor VEGF at the injury site compared to vehicle control). These results suggest that PDGF- B may play a role in regulating cellular responses in the bony repair of injured growth plate as it may stimulate infiltration of mesenchymal cells, their chondrogenic and osteogenic transforma- tion, bone formation and remodelling, and that inhibiting PDGF- receptor function causes a delay in the above injury repair responses. doi:10.1016/j.bone.2008.07.032 OR13 CCR2 deficient mice are osteopetrotic and protected from osteoporosis Nikolaus B. Binder 1 , Birgit Niederreiter 1 , Oskar Hoffmann 2 , Richard Stange 3 , Matthias Mack 4 , Thomas Pap 5 , Reinhold G. Erben 6 , Josef S. Smolen 1 , Kurt Redlich 1 1 Division of Rheumatologie, Medical University of Vienna, Austria 2 Institute of Pharmacology and Toxicology, University of Vienna, Austria 3 Department of Traumatology, University of Muenster, Germany 4 Division of Nephrology, University of Regensburg, Germany 5 Division of Molecular Medicine of Musculoskeletal Tissue, University of Muenster, Germany 6 Institute of Pathophysiology, University of Veterinary Medicine Vienna, Austria Understanding the molecular mechanisms of bone metabolism is crucial for developing novel drugs for treating diseases associated with bone loss, such as osteoporosis. Chemokines like MIP-1alpha, RANTES and MCP-1 have been shown to possess pro- S30 ABSTRACTS / Bone 43 (2008) S26–S37