4-Phenylbutyric Acid Reduces Endoplasmic Reticulum Stress in Chondrocytes That Is Caused by Loss of the Protein Disulfide Isomerase ERp57

Figure 4

4-PBA relieves ER stress in explant cultures of mouse hip and knee cartilage. (a) Immunoblot analysis of knee and hip cartilage isolated from WT mice and cultured ex vivo in explant cultures. ER marker proteins were analyzed in the presence of 10 μM Tg and different concentrations of 4-PBA. Unstimulated cartilage samples served as control and their protein/GAPDH ratios were set at 1. BiP, Chop, IRE1, and XBP1s protein levels increased in the presence of 10 μM Thapsigargin compared to the unstimulated control. The addition of 10, 20, and 50 mM 4-PBA to the Thapsigargin-stimulated explant cultures dose-dependently reduced the ER stress marker protein expression levels back to the control levels. , , , and . (b) Immunoblot analysis of knee and hip cartilage isolated from cartilage-specific ERp57 KO mice (ERp57 cKO) and cultured ex vivo in explant cultures. ER marker proteins were analyzed in the presence of 10 μM Tg and different concentrations of 4-PBA. Unstimulated cartilage samples served as a control and their protein/GAPDH ratios were set at 1. Corresponding to WT cartilage, BiP, Chop, IRE1, and XBP1s protein levels increased in ERp57 KO cartilage in the presence of 10 μM Thapsigargin compared to the unstimulated control. Likewise, the addition of 10, 20, and 50 mM 4-PBA to the Thapsigargin-stimulated explant cultures dose-dependently reduced the ER stress marker protein expression levels back to the control levels. , , , and .

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