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Osteoarthritis Cartilage ; 27(12): 1811-1821, 2019 12.
Article in English | MEDLINE | ID: mdl-31536815

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.


Subject(s)
Cartilage, Articular/drug effects , Magnesium Chloride/pharmacology , Matrix Metalloproteinase 13/drug effects , Osteoarthritis, Knee/metabolism , Synovial Membrane/drug effects , Synovitis/metabolism , 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/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 , Male , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 9/drug effects , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Meniscectomy , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Real-Time Polymerase Chain Reaction , Synovial Membrane/metabolism
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