Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
Abstract Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in vario...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2018-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-21886-w |
| _version_ | 1818430006104162304 |
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| author | Guillaume Courbon Raphaëlle Lamarque Maude Gerbaix Robin Caire Marie-Thérèse Linossier Norbert Laroche Mireille Thomas Thierry Thomas Laurence Vico Hubert Marotte |
| author_facet | Guillaume Courbon Raphaëlle Lamarque Maude Gerbaix Robin Caire Marie-Thérèse Linossier Norbert Laroche Mireille Thomas Thierry Thomas Laurence Vico Hubert Marotte |
| author_sort | Guillaume Courbon |
| collection | DOAJ |
| description | Abstract Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control values, but frizzled related protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone alterations before arthritis onset reinforce the hypothesis of an early bone involvement in arthritis. Kinetics of osteocyte markers expression should be considered to refine Wnt inhibitor treatment strategies. |
| first_indexed | 2024-12-14T15:26:32Z |
| format | Article |
| id | doaj.art-3324459e446043919c514f7d03b843cf |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:26:32Z |
| publishDate | 2018-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-3324459e446043919c514f7d03b843cf2022-12-21T22:56:00ZengNature PortfolioScientific Reports2045-23222018-02-018111010.1038/s41598-018-21886-wEarly sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis modelGuillaume Courbon0Raphaëlle Lamarque1Maude Gerbaix2Robin Caire3Marie-Thérèse Linossier4Norbert Laroche5Mireille Thomas6Thierry Thomas7Laurence Vico8Hubert Marotte9SAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonSAINBIOSE, INSERM U1059, University of LyonAbstract Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control values, but frizzled related protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone alterations before arthritis onset reinforce the hypothesis of an early bone involvement in arthritis. Kinetics of osteocyte markers expression should be considered to refine Wnt inhibitor treatment strategies.https://doi.org/10.1038/s41598-018-21886-w |
| spellingShingle | Guillaume Courbon Raphaëlle Lamarque Maude Gerbaix Robin Caire Marie-Thérèse Linossier Norbert Laroche Mireille Thomas Thierry Thomas Laurence Vico Hubert Marotte Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model Scientific Reports |
| title | Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model |
| title_full | Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model |
| title_fullStr | Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model |
| title_full_unstemmed | Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model |
| title_short | Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model |
| title_sort | early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant induced arthritis model |
| url | https://doi.org/10.1038/s41598-018-21886-w |
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