The therapeutic effects of lipoxin A4 during treadmill exercise on monosodium iodoacetate-induced osteoarthritis in rats

Mol Immunol. 2018 Nov:103:35-45. doi: 10.1016/j.molimm.2018.08.027. Epub 2018 Sep 6.

Abstract

Lipoxin A4 (LXA4), a kind of adipokines, is a potent stop signal of inflammation. Our preliminary study found that LXA4 of serum and intra-articular lavage fluid (IALF) was rapidly elevated in 2 h and rapidly reduced to normal level at 4 h after moderate-intensity treadmill exercise. The aim was to confirm the therapeutic effects of LXA4 during treadmill exercise on rat model of monosodium iodoacetate (MIA)-induced OA and the detailed mechanism of LXA4 on OA. One hundred and twenty-four male Sprague-Dawley rats were submitted to two different protocols. A single session of treadmill exercise: sixty-four rats were randomly divided into treadmill exercise of different intensities for 60 min only once (n = 4). Formal treadmill exercise: sixty rats were randomly divided into six groups (n = 10): control group (CG), knee OA group (OAG), OA with treadmill exercise of different intensities (OAL, OAM and OAH), and OAM + BOC-2 (an antagonist of LXA4 receptor). The rats were evaluated by ELISA, histology, immunohistochemistry and western blotting. Fibroblast-like synoviocytes (FLSs) were obtained from knee joint of rats. The effects of LXA4 on interleukin (IL)-1β induced FLSs were evaluated by western blotting and immunofluorescence. The results of ELISA, histological evaluation, western blotting and immunohistochemistry indicated that OAM had a better treatment which could be suppressed by BOC-2. Moreover, LXA4 could attenuate the expression of matrix metalloproteinase (MMP)-3 and MMP-13 and suppress the expression of nuclear factor-kappa B (NF-κB) p65 induced by IL-1β in FLSs. The therapeutic effects of LXA4 during treadmill exercise on MIA-induced OA via inhibiting NF-κB signaling pathway.

Keywords: Fibroblast-like synoviocyte; Lipoxin A(4); NF-κB; Osteoarthritis; Treadmill exercise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Interleukin-1beta / pharmacology
  • Iodoacetates
  • Lipoxins / blood
  • Lipoxins / metabolism
  • Lipoxins / pharmacology*
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • NF-kappa B / metabolism
  • Osteoarthritis / chemically induced
  • Osteoarthritis / physiopathology
  • Osteoarthritis / prevention & control*
  • Physical Conditioning, Animal / physiology*
  • Rats, Sprague-Dawley
  • Synoviocytes / drug effects*
  • Synoviocytes / metabolism

Substances

  • Interleukin-1beta
  • Iodoacetates
  • Lipoxins
  • NF-kappa B
  • lipoxin A4
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3