PORCN inhibition stimulates chondrocyte differentiation
| Autoři | |
|---|---|
| Rok publikování | 2019 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Porcupine (PORCN) is an endoplasmic reticulum protein belonging tothe membrane bound O–acyl transferase superfamily. This molecule isnecessary for the attachment of long chain fatty acids to WNT pro-teins. PORCN is expressed in most tissues of the body and animalswith loss of function in PORCN exhibit embryonic lethality at earlydevelopmental stages with extensive gastrulation defects. Severaldominant mutations in PORCN were described in human patients,who demonstrated significant skeletal abnormalities. Recently, a pow-erful PORCN inhibitor C59 has become commercially available andhas been successfully used to inhibit WNT pathway in several cancerlines. C59 negatively affects WNT signaling by inhibition of WNTpalmitoylation, which is necessary to acetylate WNT ligands beforetheir secretion and binding to a carrier protein. Here, we analyzed thepossible effect of this inhibitor on skeletogenesis with focus on endo-chondral bone formation. We observed, enhanced growth of mesen-chymal condensations and also increased number of cartilage nodulesin primary micromass cultures established from the early limb bud,which were treated by increasing concentrations of C59. |