Although osteoblasts express the angiogenic protein Angiopoietin 1 (Angl), the role of Angl in bone formation remains largely unknown. Here we report that Angl overexpression in osteoblasts driven by the osteoblast-specific 2.3 kb alpha 1 type 1 collagen promoter results in increased bone mass in vivo. In Angl-transgenic mice (Angl-Tg), bone volume and bone parameters increased significantly compared with wild-type littermates, although the Angl receptor, Tie2 was not expressed in osteoblasts. Tie2 is primarily expressed in vascular endothelial cells, and Angl-Tie2 signaling is reportedly crucial for angiogenesis. We found that the number of vascular endothelial cells was significantly elevated in Angl-Tg mice compared with that of wild-type littermates, an increase accompanied by increased alkaline-phosphatase activity, a marker of osteoblast activation. The number of osteoclasts in the bone of Angl-Tg mice did not differ from wild-type littermates. These results indicate that angiogenesis induced by Angl expressed in osteoblasts is coupled with osteogenesis. (C) 2007 Elsevier Inc. All rights reserved.