Osteoblast-specific Angiopoietin 1 overexpression increases bone mass.
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.
Suzuki
Toru
T
Department of Cell Differentiation, The Sakaguchi Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Miyamoto
Takeshi
T
Fujita
Nobuyuki
N
Ninomiya
Ken
K
Iwasaki
Ryotaro
R
Toyama
Yoshiaki
Y
Suda
Toshio
T
D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015519:Bone Density / Q000502:physiology*; D005269:Femur / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D015854:Up-Regulation