TY  - JOUR
T1  - Mechanisms Involved in Ceramide-Induced Autophagy in Osteoblasts
A1  - Nadia Abed Al-Hazmi
A1  - Turki Yousef Alhazzazi
A1  - Sahar Mohammed Nour Bukhary
A1  - Daniel Weekes
A1  - Fraser McDonald
A1  - Peter Hill
A1  - Agamemnon Grigoriadis
A1  - Raghad Abdullah Al-Dabbagh
JF  - Archives of Pharmacy Practice
JO  - Arch Pharm Pract
SN  - 2320-5210
Y1  - 2021
VL  - 12
IS  - 3
DO  - 10.51847/B8jiA53A5q
SP  - 125
EP  - 133
N2  - This study aimed to investigate the role of ceramide in inducing autophagy in osteoblasts, then further investigate the involved downstream signaling cascades. The effect of exogenous ceramide on inducing autophagy in MC3T3-E1 and Primary murine osteoblasts (POB) were assessed by (a) Transmission Electron Microscopy (TEM), Western Blot (WB) analysis, (c) Immunofluorescence microscopy, and (d) Propidium Iodide (PI)-uptake/flow cytometry analysis. C2-ceramide induced the formation of cytoplasmic vacuoles and elevated the expression of the autophagy proteins Atg5, beclin1, and LC3 II. Silencing Atg5 or beclin1 with siRNAs partially rescued the C2-ceramide-induced cell death in osteoblasts yet this silencing did not rescue the C2-ceramide-induced autophagy as assessed by TEM. Hence, these results suggest that C2-ceramide induces Atg5 and beclin1-independent autophagic cell death in osteoblasts. This work highlighted a novel role for ceramide in inducing autophagy in osteoblasts. The use of ceramide or inhibitors of its synthesis could be utilized as a therapeutic tool for modulating osteoblast survival in different metabolic bone diseases. 
UR  - https://archivepp.com/article/mechanisms-involved-in-ceramide-induced-autophagy-in-osteoblasts-pxfvenxzz369j4p
ER  -