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- Title
4-Phenyl butyric acid prevents glucocorticoid-induced osteoblast apoptosis by attenuating endoplasmic reticulum stress.
- Authors
Yang, Jianhui; Wu, Qiong; Lv, Jianguo; Nie, Huiyong
- Abstract
Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs) has been identified as a major cause of osteoporosis. However, the molecular mechanisms underlying GC-induced osteoporosis remain elusive. This study was conducted to make clear the mechanism of GC-induced osteoblast apoptosis and to examine whether reduction of ER stress by 4-PBA inhibited osteoblast apoptosis. After treatment with dexamethasone (Dex) or hydrocortisone, cell viability was assessed using an MTT assay. Flow cytometry was performed to assess the apoptosis of MC3T3-E1 cells. The expression levels of ER stress-related proteins (CHOP, GRP78, eIF2α, and phospho-eIF2α) and apoptosis-related proteins (cleaved Caspase-3, Bcl-2, and Bax) in MC3T3-E1 cells were measured by Western blot analysis. We found that both Dex and hydrocortisone reduced cell proliferation and promoted apoptosis in MC3T3-E1 cells. In addition, the protein expression levels of cleaved Caspase-3 and Bax increased and the protein expression level of Bcl-2 decreased in MC3T3-E1 cells exposed to Dex. In addition, the Dex exposure also resulted in a release of cytochrome c (Cyt C) from mitochondria. The cellular ATP content was decreased following prolonged treatment with Dex. 4-PBA attenuated ER stress and mitochondrial dysfunction induced by Dex in MC3T3-E1 cells. Dex-mediated apoptosis of MC3T3-E1 cells is aggravated by ER stress. Moreover, Dex-induced apoptosis in MC3T3-E1 cells was inhibited by 4-PBA, suggesting that ER stress involved in Dex-induced apoptosis. In conclusion, inhibition of ER stress by 4-PBA could reduce GC-induced apoptosis in MC3T3-E1 cells.
- Subjects
BUTYRIC acid; GLUCOCORTICOIDS; APOPTOSIS prevention; OSTEOBLASTS; ENDOPLASMIC reticulum; OSTEOPOROSIS; THERAPEUTICS; PROTEIN metabolism; OSTEOBLAST metabolism; AMINES; ANIMAL experimentation; APOPTOSIS; CELL lines; HYDROCARBONS; MICE; MITOCHONDRIA; DEXAMETHASONE; CARBOCYCLIC acids
- Publication
Journal of Bone & Mineral Metabolism, 2017, Vol 35, Issue 4, p366
- ISSN
0914-8779
- Publication type
journal article
- DOI
10.1007/s00774-016-0778-3