Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton.

Area of Science:

• Pediatric Endocrinology
• Pharmacology
• Skeletal Biology

Background:

• Angiotensin receptor blockers (ARBs) treat hypertension and show promise for Marfan and Alport syndromes.
• ARBs benefit adult bone homeostasis, but their impact on the growing pediatric skeleton is unknown.
• Investigating ARBs' effects on pediatric bone development is crucial.

Purpose of the Study:

• To investigate the effect of Losartan, an ARB, on bone mass and cartilage development in mice.
• To determine if Losartan influences osteoclastogenesis and chondrocyte activity during skeletal growth.

Main Methods:

• Wild type mice were treated with Losartan from birth to 6 weeks.
• Microcomputed tomography (microCT) and histomorphometric analyses were performed on collected bones.
• In vitro studies assessed Losartan's effect on osteoclast differentiation and ERK1/2 phosphorylation.

Main Results:

• Losartan significantly increased trabecular bone volume (98%) and cortical thickness (9%) in developing mice.
• Decreased osteoclast number and suppressed osteoclast differentiation were observed.
• Losartan treatment led to an elongated hypertrophic chondrocyte zone and increased Col10a1 expression in growth plates.

Conclusions:

• Losartan administration increases bone mass in young mice, primarily by inhibiting osteoclastogenesis.
• Losartan accelerates chondrocyte hypertrophy during skeletal development.
• These findings suggest ARBs like Losartan may have therapeutic potential for pediatric bone conditions.