Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver
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 f...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/5/471 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Adhyatmika Adhyatmika |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:40:55Z |
| format | Article |
| id | doaj.art-b319b910af32449c8e3333c092aedcec |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T19:40:55Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b319b910af32449c8e3333c092aedcec2023-11-20T01:17:38ZengMDPI AGPharmaceutics1999-49232020-05-0112547110.3390/pharmaceutics12050471Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine LiverAdhyatmika Adhyatmika0Leonie Beljaars1Kurnia S. S. Putri2Habibie Habibie3Carian E. Boorsma4Catharina Reker-Smit5Theerut Luangmonkong6Burak Guney7Axel Haak8Keri A. Mangnus9Eduard Post10Klaas Poelstra11Kim Ravnskjaer12Peter Olinga13Barbro N. Melgert14Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 M Odense M, DenmarkDepartment of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsDepartment of Molecular Pharmacology, Groningen Research Institute for Pharmacy, University of Groningen, 9713 AV Groningen, The NetherlandsOsteoprotegerin (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.https://www.mdpi.com/1999-4923/12/5/471cirrhosisTGFβ1CCl<sub>4</sub>resolutionhepatic stellate cellsosteoprotegerin |
| spellingShingle | 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 Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver Pharmaceutics cirrhosis TGFβ1 CCl<sub>4</sub> resolution hepatic stellate cells osteoprotegerin |
| title | Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver |
| title_full | Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver |
| title_fullStr | Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver |
| title_full_unstemmed | Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver |
| title_short | Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver |
| title_sort | osteoprotegerin is more than a possible serum marker in liver fibrosis a study into its function in human and murine liver |
| topic | cirrhosis TGFβ1 CCl<sub>4</sub> resolution hepatic stellate cells osteoprotegerin |
| url | https://www.mdpi.com/1999-4923/12/5/471 |
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