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In vitro and in vivo assessment of the proresolutive and antiresorptive actions of resolvin D1: relevance to arthritis
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In vitro and in vivo assessment of the proresolutive and antiresorptive actions of resolvin D1: relevance to arthritis
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Journal Article
In vitro and in vivo assessment of the proresolutive and antiresorptive actions of resolvin D1: relevance to arthritis
2019
Overview
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-1β, IFN-γ, PGE
2
, 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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Arthritis, Experimental - metabolism
/ Arthritis, Experimental - physiopathology
/ Arthritis, Experimental - prevention & control
/ Bone and Bones - drug effects
/ Cell Differentiation - drug effects
/ Cell Survival - drug effects
/ Docosahexaenoic Acids - pharmacology
/ Female
/ Humans
/ Inflammation Mediators - metabolism
/ Leukocytes, Mononuclear - cytology
/ Leukocytes, Mononuclear - drug effects
/ Leukocytes, Mononuclear - metabolism
/ Medicine
/ Mice
