Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model.
Sci Rep
; 8(1): 3492, 2018 02 22.
Article
em En
| MEDLINE
| ID: mdl-29472591
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Artrite Experimental
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Artrite Reumatoide
/
Marcadores Genéticos
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Proteínas Morfogenéticas Ósseas
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Peptídeos e Proteínas de Sinalização Intercelular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2018
Tipo de documento:
Article