Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis

• Published in: Scientific reports 2017-05, Vol.7 (1), p.2293-11, Article 2293
• Main Authors: Abuohashish, Hatem M., Ahmed, Mohammed M., Sabry, Dina, Khattab, Mahmoud M., Al-Rejaie, Salim S.
• Format: Article
• Language: English
• Subjects: 59; 692/163/2743/316/801; 692/308/1426; 692/4017; 82/1; 82/58; 82/80; ACE2; Angiotensin; Angiotensin I - pharmacology; Angiotensin II; Angiotensin-converting enzyme 2; Animals; Blotting, Western; Bone turnover; Degeneration; Female; Humanities and Social Sciences; Humans; Metabolism; Minerals; Morphometry; multidisciplinary; NF-κB protein; Organ Size - drug effects; Osteoporosis; Osteoporosis - etiology; Osteoporosis - metabolism; Osteoporosis - prevention & control; Osteoprotegerin; Osteoprotegerin - metabolism; Ovariectomy; Ovariectomy - adverse effects; Peptide Fragments - pharmacology; Peptidyl-Dipeptidase A - metabolism; Proto-Oncogene Proteins - metabolism; RANK Ligand - metabolism; Rats, Wistar; Receptor mechanisms; Receptors, G-Protein-Coupled - metabolism; Renin; Rodents; Science; Science (multidisciplinary); Signal Transduction - drug effects; Skeletal system; TRANCE protein; Uterus - drug effects; Uterus - pathology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-02570-x

The local and systemic renin angiotensin system (RAS) influences the skeletal system micro-structure and metabolism. Studies suggested angiotensin 1-7 (Ang(1-7)) as the beneficial RAS molecule via Mas receptor activation. This study examines the function of Ang(1-7) in bone micro-architecture and metabolism in an ovariectomized (OVX) rodent model of osteoporosis. OVX rats showed structural and bone metabolic degeneration in parallel with suppressed expressions of the angiotensin converting enzyme-2 (ACE-2)/Ang(1-7)/Mas components. The infusion of Ang(1-7) markedly alleviated the altered bone metabolism and significantly enhanced both trabecular (metaphyseal) and cortical (metaphyseal-diaphyseal) morphometry. Urinary and bones minerals were also improved in OVX rats by Ang(1-7). The infusion of the heptapeptide enhanced ACE-2/Mas receptor expressions, while down-regulated AngII, ACE, and AngII type-1 receptor (AT1R) in OVX animals. Moreover, Ang(1-7) markedly improved osteoprotegerin (OPG) and lowered receptor activator NF-κB ligand (RANKL) expressions. The defensive properties of Ang(1-7) on bone metabolism, structure and minerals were considerably eradicated after blockage of Mas receptor with A-779. Ang(1-7)-induced up-regulated ACE-2/Ang(1-7)/Mas cascade and OPG expressions were abolished and the expressions of ACE/AngII/AT1R and RANKL were provoked by A-779. These findings shows for the first time the novel valuable therapeutic role of Ang(1-7) on bone health and metabolism through the ACE-2/Mas cascade.