FIGURE

Figure 5

ID
ZDB-FIG-201107-30
Publication
Lu et al., 2020 - Inappropriate cathepsin K secretion promotes its enzymatic activation driving heart and valve malformation
Other Figures
All Figure Page
Back to All Figure Page
Figure 5

Treatment with the cathepsin K inhibitor odanacatib rescues MLII heart defects.

(A and B) Confocal analyses of tie2:EGFP+ (green) hearts stained immunohistochemically for myosin (red) show that treatment with 50 nM odanacatib restores normal morphology to MLII hearts and valves, as assayed by the number of MLII embryos with hearts that loop and valves that open and close (“clap”) at regular intervals following treatment. Percent values on images represent the number of embryos with the pictured phenotype. n = 100–125 embryos. Data are presented as mean ± SEM. **P < 0.01,***P < 0.001, ****P < 0.0001 using Dunnett’s test with correction (indicated by red box). Each dot represents the average of 20–25 embryos from 4–5 experiments. Scale bar: 25 μm. (C) In situ analyses of notch1b expression show restored differentiation of MLII valve cells (red arrowheads) following treatment with odanacatib. Percent values represent the number of embryos with the pictured phenotype. n = 75 embryos from 3 experiments. Scale bar: 50 μm. (D) Confocal analyses of embryos stained immunhistochemically for myosin (red) and pSmad1/5/8 (green) show odanacatib treatment increases BMP signaling in MLII embryos. Panels to the right represent higher-power images of boxed regions; white arrowheads denote nuclear localized pSmad1/5/8. Scale bar: 20 μm. (E) Graphs show percent cells containing Smad+ nuclei in WT, gnptab morphant, and odanacatib-treated embryos. n = 20–25 embryos imaged from 3 experiments. Data are presented as mean ± SEM. Student’s t test. **P < 0.01, ***P < 0.001. (F) Confocal images of myl7:RFP+ (labels cardiomyocytes red) and BRE:dsEGFP+ (green) embryos confirm odanacatib treatment improves BMP signaling in MLII embryos. Data quantified in Supplemental Figure 2. n = 10–15 embryos imaged from 2 experiments. Scale bar: 30 μm.

Expression Data
Gene:
Antibodies:
Fish:
Condition:
Knockdown Reagents:
Anatomical Terms:
Stage: Day 4

Expression Detail
Antibody Labeling
Phenotype Data
Fish:
Condition:
Knockdown Reagents:
Observed In:
Stage: Day 4

Phenotype Detail
Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ JCI Insight