CITED2 mediates cross-talk between mechanical loading and IL-4 and results in synergistic chondroprotection in vitro and in vivo Z. He, D.J. Leong, L.

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CITED2 mediates cross-talk between mechanical loading and IL-4 and results in synergistic chondroprotection in vitro and in vivo Z. He, D.J. Leong, L. Xu, J.A. Hardin, R.J. Majeska, M.B. Schaffler, M.M. Thi, L. Cardoso, M.B. Goldring, N.J. Cobelli, H.B. Sun Osteoarthritis and Cartilage Volume 23, Pages A62-A63 (April 2015) DOI: 10.1016/j.joca.2015.02.130 Copyright © 2015 Terms and Conditions

Figure 1. IL-4 includes CITED2 mRNA expression in a (A) dose and (B) time-dependent manner in human C28/I2 chondrocytic cells. (C) IL-4-induced is suppressed by Jak3 and STAT6 inhibitors and (D) CITED2 upregulation is associated with phosphorylation of Jak3 and STAT6, as revealed by real-time PCR and Western blot, respectively. Osteoarthritis and Cartilage 2015 23, A62-A63DOI: (10.1016/j.joca.2015.02.130) Copyright © 2015 Terms and Conditions

Figure 2. A low dose of IL-4 combined with either (A) uniaxial tensile strain or (B) IHP synergistically induces CITED2 mRNA and suppresses MMP-13 mRNA. (C) These effects are abolished by CITED2 knocked down in C28/I2 chondrocytes transfected with CITED2 siRNA in the presence of IL-1β. Osteoarthritis and Cartilage 2015 23, A62-A63DOI: (10.1016/j.joca.2015.02.130) Copyright © 2015 Terms and Conditions

Figure 3 (A) Moderate treadmill running-suppressed Mmp-13 expression in the articular cartilage is diminished in IL4KO mice and completely abolished in IL4KO mice with Cited2 knocked down. (B) DMM mice subjected to IL-4 and cage activity (cage) exhibited efficacy in chondroprotection The chondroprotective effect was diminished in DMM + IL-4 mice when the hind limb was immobilized (Imm, deloading). White arrows indicate regions cartilage erosion or loss of proteoglycans. Osteoarthritis and Cartilage 2015 23, A62-A63DOI: (10.1016/j.joca.2015.02.130) Copyright © 2015 Terms and Conditions