Intra-articular injection of magnesium chloride attenuates osteoarthritis progression in rats

Osteoarthritis Cartilage. 2019 Dec;27(12):1811-1821. doi: 10.1016/j.joca.2019.08.007. Epub 2019 Sep 16.

Abstract

Objective: To explore the effects of Mg2+ on the expression of osteoarthritic markers in human cartilage and synovium tissue explants. To investigate the therapeutic effect of intra-articular injection of Mg2+ in an established rat OA (Osteoarthritis) model of anterior cruciate ligament transection with partial medial meniscectomy (ACLT + PMM).

Design: Human cartilage and synovium explants were collected from total knee replacement surgeries and incubated with MgCl2 (20 mmol/L) in vitro. A rat OA model was established by ACLT + PMM surgery in 450-500 g male Sprague Dawley (SD) rats. To select the optimal dose, intra-articular injections of MgCl2 (0.05, 0.5, 5 mol/L) were performed at 4 weeks after the surgery every 3 days for 2 weeks. The effect of optimized MgCl2 was further determined by histology, immunohistochemistry, and quantitative real-time polymerase chain reaction.

Results: The expressions of osteoarthritic markers in human cartilage and synovium explants were inhibited by Mg2+in vitro. Immunohistochemical analysis further suggested the inhibitory effects of Mg2+ on the expression of MMP-13 and IL-6 in the human tissue explants. Cartilage degeneration and synovitis in ACLT + PMM rats were significantly improved by intra-articular injections of Mg2+ (0.5 mol/L). Immunohistochemical analysis also showed the regulatory effects of Mg2+ on osteoarthritic markers in both cartilage and synovium in rats, consistent with in vitro results.

Conclusion: Intra-articular injections of Mg2+ at 0.5 mol/L attenuate the progression of OA in the ACLT + PMM rat model. Such effect was at least in part explained by the promotion of cartilage matrix synthesis and the suppression of synovial inflammation.

Keywords: Cartilage; Inflammation; Magnesium; Osteoarthritis; Synovium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS Proteins / drug effects
  • ADAMTS Proteins / genetics
  • ADAMTS Proteins / metabolism
  • Aged
  • Aggrecans / drug effects
  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Animals
  • Anterior Cruciate Ligament / surgery
  • Arthroplasty, Replacement, Knee
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Collagen Type II / drug effects
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Injections, Intra-Articular
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Magnesium Chloride / pharmacology*
  • Male
  • Matrix Metalloproteinase 13 / drug effects*
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Meniscectomy
  • Osteoarthritis, Knee / metabolism*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism
  • Synovitis / metabolism*

Substances

  • Aggrecans
  • Collagen Type II
  • Interleukin-1beta
  • Interleukin-6
  • RNA, Messenger
  • Magnesium Chloride
  • ADAMTS Proteins
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 9