In vitro and in vivo assessment of the proresolutive and antiresorptive actions of resolvin D1: relevance to arthritis.
Arthritis Res Ther
; 21(1): 72, 2019 03 12.
Article
em En
| MEDLINE
| ID: mdl-30867044
ABSTRACT
BACKGROUND:
Resolvin D1 (RvD1), an important member of resolvins, exerts a wide spectrum of biological effects, including resolution of inflammation, tissue repair, and preservation of cell viability. The aim of the present study is to investigate the anti-arthritic potential and clarify the bone protective actions of RvD1 in vitro and in vivo.METHODS:
RAW264.7 cells were treated with 50 ng/ml LPS for 72 h in the presence or absence of RvD1 (0-500 nM). Primary human monocytes were treated with M-CSF + RANKL for 14 days ± RvD1 (0-500 nM) with or without siRNA against RvD1 receptor FPR2. Expressions of inflammatory mediators, degrading enzymes, osteoclasts (OC) formation, and bone resorption were analyzed. The therapeutic effect of RvD1 (0-1000 ng) was carried out in murine collagen antibody-induced arthritis. Arthritis scoring, joint histology, and inflammatory and bone turnover markers were measured.RESULTS:
RvD1 is not toxic and inhibits OC differentiation and activation. It decreases bone resorption, as assessed by the inhibition of TRAP and cathepsin K expression, hydroxyapatite matrix resorption, and bone loss. In addition, RvD1 reduces TNF-α, IL-1ß, IFN-γ, PGE2, and RANK and concurrently enhances IL-10 in OC. Moreover, in arthritic mice, RvD1 alleviates clinical score, paw inflammation, and bone and joint destructions. Besides, RvD1 reduces inflammatory mediators and markedly decreases serum markers of bone and cartilage turnover.CONCLUSION:
Our results provide additional evidence that RvD1 plays a key role in preventing bone resorption and other pathophysiological changes associated with arthritis. The study highlights the clinical relevance of RvD1 as a potential compound for the treatment of inflammatory arthritis and related bone disorders.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
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Leucócitos Mononucleares
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Redução de Peso
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Ácidos Docosa-Hexaenoicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article