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Title: Osteoprotegerin is more than a possible serum marker in liver fibrosis: A study into its function in human and murine liver
Authors: Adhyatmika Adhyatmika
Leonie Beljaars
Kurnia S.S. Putri
Habibie Habibie
Carian E. Boorsma
Catharina Reker‐smit
Theerut Luangmonkong
Burak Guney
Axel Haak
Keri A. Mangnus
Eduard Post
Klaas Poelstra
Kim Ravnskjaer
Peter Olinga
Barbro N. Melgert
Hasanuddin University
Universitas Gadjah Mada
Universitas Indonesia
Syddansk Universitet
Mahidol University
University of Groningen
University of Groningen, University Medical Center Groningen
Keywords: Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-May-2020
Citation: Pharmaceutics. Vol.12, No.5 (2020)
Abstract: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Osteoprotegerin (OPG) serum levels are associated with liver fibrogenesis and have been proposed as a biomarker for diagnosis. However, the source and role of OPG in liver fibrosis are unknown, as is the question of whether OPG expression responds to treatment. Therefore, we aimed to elucidate the fibrotic regulation of OPG production and its possible function in human and mouse livers. OPG levels were significantly higher in lysates of human and mouse fibrotic livers compared to healthy livers. Hepatic OPG expression localized in cirrhotic collagenous bands in and around myofibroblasts. Single cell sequencing of murine liver cells showed hepatic stellate cells (HSC) to be the main producers of OPG in healthy livers. Using mouse precision‐cut liver slices, we found OPG production induced by transforming growth factor β1 (TGFβ1) stimulation. Moreover, OPG itself stimulated expression of genes associated with fibrogenesis in liver slices through TGFβ1, suggesting profibrotic activity of OPG. Resolution of fibrosis in mice was associated with decreased production of OPG compared to ongoing fibrosis. OPG may stimulate fibrogenesis through TGFβ1 and is associated with the degree of fibrogenesis. It should therefore be investigated further as a possible drug target for liver fibrosis or biomarker for treatment success of novel antifibrotics.
ISSN: 19994923
Appears in Collections:Scopus 2020

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