Azilsartan inhibits inflammation-triggered bone resorption and osteoclastogenesis in vivo via suppression of TNF-α expression in macrophages

Introduction Hypertension is a major risk factor for cardiovascular disease (CVD) and associated with increased bone loss due to excessive activity of the local renin-angiotensin system (RAS). Angiotensinogen/Angiotensin (ANG) II/Angiotensin II type 1 receptor (AT1R) axis considered as core regulating RAS activity. Azilsartan an FDA-approved selective AT1R antagonist that used treat hypertension. This study aimed determine whether azilsartan affects formation osteoclast, resorption bone, expression cytokines linked osteoclastogenesis during lipopolysaccharide (LPS)-triggered inflammation in vivo . Methods In , following 5-day supracalvarial injection LPS or tumor necrosis factor-alpha (TNF-α) without azilsartan, proportion number tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, which are identified osteoclasts on mice calvariae were counted. The mRNA levels TRAP, cathepsin K, activator NF-κB ligand (RANKL), TNF-α also evaluated. vitro effect (0, 0.01, 0.1, 1, 10 μM) RANKL TNF-α-triggered investigated. Also, restrains LPS-triggered protein macrophages osteoblasts assessed. Furthermore, western blotting analysis mitogen-activated kinases (MAPKs) signaling was conducted. Results Azilsartan-treated exhibited significantly lower than those treated alone. administration resulted Nevertheless, did not show inhibitory RANKL- Compared LPS, by azilsartan. contrast, same cells co-treated exposed only. suppressed MAPKs pathway macrophages. After injection, there no difference between group group. Conclusion These findings imply prevents production macrophages, turn LPS-Triggered osteoclast