Wnt pathway inhibition with the porcupine inhibitor LGK974 decreases trabecular bone but not fibrosis in a murine model with fibrotic bone.

ABSTRACT: G protein-coupled receptors (GPCRs) mediate a wide spectrum of physiological functions, including the development, remodeling, and repair of the skeleton. Fibrous dysplasia (FD) of the bone is characterized by fibrotic, expansile bone lesions caused by activating mutations in GNAS. There are no effective therapies for FD. We previously showed that ColI(2.3)⁺/Rs1⁺ mice, in which G_s-GPCR signaling was hyper-activated in osteoblastic cell lineages using an engineered receptor strategy, developed a fibrotic bone phenotype with trabecularization that could be reversed by normalizing G_s-GPCR signaling, suggesting that targeting the G_s-GPCR or components of the downstream signaling pathway could serve as a promising therapeutic strateg

SUBMITTER: Lung H 

PROVIDER: S-EPMC10994528 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature