Osteoblast-specific Angiopoietin 1 overexpression increases bone mass

Department of Orthopedic Surgery, Keio University, Edo, Tōkyō, Japan
Biochemical and Biophysical Research Communications (Impact Factor: 2.28). 12/2007; 362(4):1019-25. DOI: 10.1016/j.bbrc.2007.08.099
Source: PubMed

ABSTRACT Although osteoblasts express the angiogenic protein Angiopoietin 1 (Ang1), the role of Ang1 in bone formation remains largely unknown. Here we report that Ang1 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 Ang1-transgenic mice (Ang1-Tg), bone volume and bone parameters increased significantly compared with wild-type littermates, although the Ang1 receptor, Tie2 was not expressed in osteoblasts. Tie2 is primarily expressed in vascular endothelial cells, and Ang1-Tie2 signaling is reportedly crucial for angiogenesis. We found that the number of vascular endothelial cells was significantly elevated in Ang1-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 Ang1-Tg mice did not differ from wild-type littermates. These results indicate that angiogenesis induced by Ang1 expressed in osteoblasts is coupled with osteogenesis.

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    • "The importance of Ang1 in these processes is supported by the observation that adding excessive Ang1 promotes bone formation, whereas blocking Tie2, the angiopoietin receptor, inhibits vascular ingrowth and delays or disrupts regeneration. In addition, osteoblast‐mediated overexpression of Ang1 reportedly increases ALP activity and bone mass in vivo, suggesting that Ang1 is also coupled to bone formation [Suzuki et al., 2007]. Furthermore, increased Ang1 expression during angiogenesis‐induced chondrocyte maturation involving endochondral ossification has been demonstrated [Fang et al., 2005; Jeong et al., 2010; Park et al., 2010]. "
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