Losartan alters osteoblast differentiation and increases bone mass through inhibition of TGF

Excessive production of Transforming Growth Factor β (TGFβ) is commonly associated with dominant and recessive forms of OI. Previous reports have indicated that administration of TGFβ-targeted antibodies maybe of potential therapeutic benefit to OI patients. However, direct targeting of TGFβ is likely to cause multiple adverse effects including simulation of autoimmunity. In the current study we use patient-derived normal and OI fibroblasts, osteoblasts and OIM mouse models to determine the effects of Losartan, an angiotensin II receptor type 1 (AT1) antagonist, on TGFβ signalling and bone morphology in OI. In OIM mice bred on a mixed background administration of 0.6 g/L losartan for 4 weeks was associated with a significant reduction in TGFβ from 79.2 g/L in the control to 60.0 ng/ml following losartan (

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© 2024 The Authors.

Déclaration de conflit d'intérêts

NJB is global chief investigator of the Ultragenyx-funded studies (ORBIT, COSMIC) of setrusumab in children and young adults with OI and has consulted with Alexion, Mereo and Rampart and has been DMEC chair for a Pfizer study (recifercept in achondroplasia). No other authors have relevant conflicts of interest to declare.