Angiotensin II Type 2 Receptor Blockade Increases Bone Mass

• Published in: The Journal of biological chemistry Vol. 284; no. 8; pp. 4857 - 4864
• Main Authors: Izu, Yayoi, Mizoguchi, Fumitaka, Kawamata, Aya, Hayata, Tadayoshi, Nakamoto, Testuya, Nakashima, Kazuhisa, Inagami, Tadashi, Ezura, Yoichi, Noda, Masaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-02-2009; American Society for Biochemistry and Molecular Biology
• Subjects: Angiotensin II Type 2 Receptor Blockers; Animals; Blood Pressure - drug effects; Blood Pressure - physiology; Bone and Bones - cytology; Bone and Bones - metabolism; Bone Development - drug effects; Bone Development - physiology; Humans; Imidazoles - pharmacology; Male; Mice; Mice, Knockout; Organ Size - drug effects; Organ Size - physiology; Osteoblasts - cytology; Osteoblasts - metabolism; Osteoclasts - cytology; Osteoclasts - metabolism; Pyridines - pharmacology; Receptor, Angiotensin, Type 2 - metabolism; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Vasoconstrictor Agents - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M807610200

Renin angiotensin system (RAS) regulates circulating blood volume and blood pressure systemically, whereas RAS also plays a role in the local milieu. Previous in vitro studies suggested that RAS may be involved in the regulation of bone cells. However, it was not known whether molecules involved in RAS are present in bone in vivo. In this study, we examined the presence of RAS components in adult bone and the effects of angiotensin II type 2 (AT2) receptor blocker on bone mass. Immunohistochemistry revealed that AT2 receptor protein was expressed in both osteoblasts and osteoclasts. In addition, renin and angiotensin II-converting enzyme were expressed in bone cells in vivo. Treatment with AT2 receptor blocker significantly enhanced the levels of bone mass, and this effect was based on the enhancement of osteoblastic activity as well as the suppression of osteoclastic activity in vivo. These results indicate that RAS components are present in adult bone and that blockade of AT2 receptor results in alteration in bone mass.