Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton

Molecular Genetics and Metabolism
Shan ChenYangjin Bae

Abstract

Angiotensin receptor blockers (ARBs) are a group of anti-hypertensive drugs that are widely used to treat pediatric hypertension. Recent application of ARBs to treat diseases such as Marfan syndrome or Alport syndrome has shown positive outcomes in animal and human studies, suggesting a broader therapeutic potential for this class of drugs. Multiple studies have reported a benefit of ARBs on adult bone homeostasis; however, its effect on the growing skeleton in children is unknown. We investigated the effect of Losartan, an ARB, in regulating bone mass and cartilage during development in mice. Wild type mice were treated with Losartan from birth until 6 weeks of age, after which bones were collected for microCT and histomorphometric analyses. Losartan increased trabecular bone volume vs. tissue volume (a 98% increase) and cortical thickness (a 9% increase) in 6-weeks old wild type mice. The bone changes were attributed to decreased osteoclastogenesis as demonstrated by reduced osteoclast number per bone surface in vivo and suppressed osteoclast differentiation in vitro. At the molecular level, Angiotensin II-induced ERK1/2 phosphorylation in RAW cells was attenuated by Losartan. Similarly, RANKL-induced ERK1/2 phosphorylation w...Continue Reading

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Citations

Dec 15, 2015·Development·Eva S LiuMarie B Demay
Sep 29, 2018·Clinical Oral Implants Research·Gabriel Mulinari-SantosRoberta Okamoto
Oct 16, 2016·Journal of Inherited Metabolic Disease·Mark J OsbornElizabeth A Braunlin
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Feb 10, 2019·International Journal of Molecular Sciences·Luc RochetteCatherine Vergely
Oct 10, 2019·Journal of Applied Oral Science : Revista FOB·Gabriel Mulinari-SantosRoberta Okamoto

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