In vitro and in vivo assessment of the proresolutive and antiresorptive actions of resolvin D1: relevance to arthritis

  • Arthritis Res Ther. 2019 Mar 12;21(1):72. doi: 10.1186/s13075-019-1852-8.
Houda Abir Benabdoun  1  2 ,  Merve Kulbay  2 ,  Elsa-Patricia Rondon  2 ,  Francis Vallières  2 ,  Qin Shi  2 ,  Julio Fernandes  2  3 ,  Hassan Fahmi  4  5 ,  Mohamed Benderdour  6  7
Affiliations
  • 1. Department of Pharmacology, Université de Montréal, Montreal,, QC, Canada.
  • 2. Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada.
  • 3. Department of Surgery, Université de Montréal, Montreal, QC, Canada.
  • 4. Osteoarthritis Research Unit, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.
  • 5. Department of Medicine, University of Montreal, Montreal, QC, Canada.
  • 6. Orthopedic Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada. [email protected].
  • 7. Department of Surgery, Université de Montréal, Montreal, QC, Canada. [email protected].
PMID: 30867044 DOI: 10.1186/s13075-019-1852-8
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-1β, 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.

Keywords
Arthritis; Bone resorption; Inflammation; Mice; Resolvin D1.
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