Salubrinal reduces expression and activity of MMP13 in chondrocytes

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Presentation transcript:

Salubrinal reduces expression and activity of MMP13 in chondrocytes K. Hamamura, C.-C. Lin, H. Yokota Osteoarthritis and Cartilage Volume 21, Issue 5, Pages 764-772 (May 2013) DOI: 10.1016/j.joca.2013.02.657 Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Responses of C28/I2 chondrocytes to tunicamycin and salubrinal. (A) Cell mortality ratio. (B) Relative cell number. (C) Elevation of the level of cleaved caspase 3, which was reduced by salubrinal. (D) Relative mRNA abundance of CHOP. (E) Relative mRNA abundance of MMP13. Osteoarthritis and Cartilage 2013 21, 764-772DOI: (10.1016/j.joca.2013.02.657) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Western blot analysis for eIF2α, p38 MAPK, and NFκB to tunicamycin. (A) Elevation of p-eIF2α and ATF4. (B) Upregulation of p-p38 MAPK by tunicamycin and its partial suppression by 10 μM salubrinal. (C) No effects on NFκB signaling by tunicamycin. The positive controls for p-IKKα/β and p-NFκB are shown in response to 10 ng/ml TNFα and 1 ng/ml IL1β. Osteoarthritis and Cartilage 2013 21, 764-772DOI: (10.1016/j.joca.2013.02.657) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Responses of C28/I2 and primary chondrocytes to TNFα. (A) Cell mortality ratio in C28/I2 chondrocytes. (B) Relative cell number in C28/I2 chondrocytes. (C) Relative MMP13 mRNA abundance to TNFα in C28/I2 chondrocytes. (D) MMP13 activity induced by TNFα and suppressed by 5 μM salubrinal in C28/I2 chondrocytes. (E) MMP13 activity induced by TNFα and suppressed by 5 μM salubrinal in primary chondrocytes. (F) Elevation of p-p38 MAPK by TNFα, which is partially decreased by 5 μM salubrinal. (G–H) Activation of NFκB by TNFα and partial de-activation by salubrinal in C28/I2 chondrocytes and primary chondrocytes, respectively. Osteoarthritis and Cartilage 2013 21, 764-772DOI: (10.1016/j.joca.2013.02.657) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Responses of C28/I2 chondrocytes to IL1β. (A) Cell mortality ratio. (B) Relative cell number. (C) Relative MMP13 mRNA abundance in response to IL1β. (D) MMP13 activity induced by IL1β and suppressed by 10 μM salubrinal. (E) Elevation of p-p38 MAPK by IL1β, which is partially decreased by 10 μM salubrinal. (F) Activation of NFκB by IL1β and its partial suppression by 10 μM salubrinal. Osteoarthritis and Cartilage 2013 21, 764-772DOI: (10.1016/j.joca.2013.02.657) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 5 Effects of silencing NFκB p65 (RelA) in C28/I2 chondrocytes. (A) Western blots for silencing NFκB p65. (B) Effects of silencing RelA on p-NFκB, p-p38 MAPK and p-eIF2α. (C) Suppression of TNFα driven upregulation of MMP13 activity by silencing NFκB p65. Osteoarthritis and Cartilage 2013 21, 764-772DOI: (10.1016/j.joca.2013.02.657) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 6 Effects of IL1β, tunicamycin, and salubrinal on the mRNA levels of MMPs. (A–D) Messenger RNA levels of MMP1, MMP2, MMP3, and MMP14 in response to IL1β, respectively. (E–H) Messenger RNA levels of MMP1, MMP2, MMP3, and MMP14 in response to tunicamycin, respectively. Osteoarthritis and Cartilage 2013 21, 764-772DOI: (10.1016/j.joca.2013.02.657) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 7 Potential signaling pathways involved in the regulation of MMP13 in response to ER stress and inflammatory cytokines. Osteoarthritis and Cartilage 2013 21, 764-772DOI: (10.1016/j.joca.2013.02.657) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions