Intra-articular injection of interleukin-4 decreases nitric oxide production by chondrocytes and ameliorates subsequent destruction of cartilage in instability-induced osteoarthritis in rat knee joints

Osteoarthritis and Cartilage
M YorimitsuT Ozaki

Abstract

To investigate the in vitro and in vivo effects of interleukin (IL)-4 on mechanical stress-induced nitric oxide (NO) expression by chondrocytes, and destruction of cartilage and NO production in an instability-induced osteoarthritis (OA) model in rat knee joints, respectively. Cyclic tensile stress (CTS; 0.5Hz and 7% elongation) was applied to cultured normal rat chondrocytes with or without pre-incubation with recombinant rat IL-4 (rrIL-4). Inducible NO synthase (iNOS) mRNA expression and NO production were examined with real-time polymerase chain reaction and the Griess reaction, respectively. OA was induced in rat knee joints by transection of the anterior cruciate and medial collateral ligaments and resection of the medial meniscus. rrIL-4 (10, 50, and 100 ng/joint/day) was injected intra-articularly, and knee joint samples were collected 2, 4, and 6 weeks after surgery. Cartilage destruction was evaluated by the modified Mankin score and Osteoarthritis Research Society International scoring system on paraffin-embedded sections stained with safranin O. Cleavage of aggrecan and NO production were examined by immunohistochemistry for aggrecan neoepitope (NITEGE) and of nitrotyrosine (NT), respectively. rrIL-4 down-regulated C...Continue Reading

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