Sprifermin (rhFGF18) versus vehicle induces a biphasic process of extracellular matrix remodeling in human knee OA articular cartilage ex vivo
| Autor: | Thorbjørn Gantzel, D. Reker, Anne Sofie Siebuhr, Anders Aspberg, Anne-Christine Bay-Jensen, Morten A. Karsdal, Christoph Ladel, Anne Gigout, Christian S. Thudium, M. Michaelis, M. W. Berchtold |
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| Rok vydání: | 2020 |
| Předmět: |
Cartilage
Articular Male 0301 basic medicine Type II collagen lcsh:Medicine Osteoarthritis Article Target validation Extracellular matrix Andrology Prognostic markers 03 medical and health sciences Chondrocytes 0302 clinical medicine medicine Humans lcsh:Science Collagen Type II Aggrecan Aggrecanase 030203 arthritis & rheumatology Multidisciplinary biology Chemistry Cartilage lcsh:R Osteoarthritis Knee medicine.disease Drug regulation Extracellular Matrix Fibroblast Growth Factors 030104 developmental biology medicine.anatomical_structure Proteoglycan biology.protein Female Proteoglycans lcsh:Q Sprifermin |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020) Reker, D, Siebuhr, A S, Thudium, C S, Gantzel, T, Ladel, C, Michaelis, M, Aspberg, A, Berchtold, M W, Karsdal, M A, Gigout, A & Bay-Jensen, A C 2020, ' Sprifermin (rhFGF18) versus vehicle induces a biphasic process of extracellular matrix remodeling in human knee OA articular cartilage ex vivo ', Scientific Reports, vol. 10, 6011 . https://doi.org/10.1038/s41598-020-63216-z Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-63216-z |
| Popis: | Sprifermin, recombinant human fibroblast growth factor 18 (rhFGF18), induces cartilage regeneration in knees of patients with osteoarthritis (OA). We hypothesized that a temporal multiphasic process of extracellular matrix (ECM) degradation and formation underlie this effect. We aimed to characterize the temporal ECM remodeling of human knee OA articular cartilage in response to sprifermin treatment. Articular cartilage explants from patients with knee OA (npatients = 14) were cultured for 70 days, with permanent exposure to sprifermin (900, 450, 225 ng/mL), FGF18 (450 ng/mL), insulin-like growth factor-1 (100 ng/mL, positive control) or vehicle (nreplicates/treatment/patient = 2). Metabolic activity (AlamarBlue) and biomarkers of type IIB collagen (PIIBNP) formation (Pro-C2 enzyme-linked immunosorbent assay [ELISA]) and aggrecanase-mediated aggrecan neo-epitope NITEGE (AGNx1 ELISA) were quantified once a week. At end of culture (day 70), gene expression (quantitative reverse transcription polymerase chain reaction) and proteoglycan content (Safranin O/Fast green staining) were quantified. The cartilage had continuously increased metabolic activity, when treated with sprifermin/FGF18 compared to vehicle. During days 7–28 PIIBNP was decreased and NITEGE was increased, and during days 35–70 PIIBNP was increased. At end of culture, the cartilage had sustained proteoglycan content and relative expression of ACAN |
| Databáze: | OpenAIRE |
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