Glucocorticoid-Induced Osteocytic Cell Death in a Hypoxic Environment Is Associated with Necroptosis
| Autor: | Yoshimichi Ueda, Miyako Shimasaki, Hiroaki Hirata, Norio Kawahara, Shusuke Ueda, Toru Ichiseki |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
dexamethasone (Dex)
Programmed cell death Chemistry Necroptosis osteonecrosis Cell necroptosis receptor-interacting protein 1 (RIP1) General Medicine Hypoxia (medical) Blot necrostatin-1 (Nec-1) medicine.anatomical_structure In vivo Apoptosis receptor-interacting protein 3 (RIP3) medicine Cancer research medicine.symptom Glucocorticoid medicine.drug |
| Zdroj: | BioChem Volume 1 Issue 2 Pages 9-106 |
| ISSN: | 2673-6411 |
| Popis: | Neither the underlying pathophysiology of nor prophylactic strategies for glucocorticoid-associated femoral head osteonecrosis have yet been established. In neurovascular and cardiac ischemic disorders, necroptosis has been reported as a new concept of cell death. Here we investigated the involvement of necroptosis in glucocorticoid-induced osteonecrosis in vitro, the putative cause of which is ischemia. Murine osteocytic cells (MLO-Y4) to which 1 µM dexamethasone (Dex) was added and were cultured in 1% O2 (hypoxia) are thought to resemble the in vivo environment in which glucocorticoid-induced osteonecrosis occurs (H-D stress environment). Using such cells cultured for 24 h (Dex(+)/hypoxia(+) group), immunofluorescent staining and Western blotting were performed with receptor-interacting protein (RIP) 1 and RIP3, which are necroptosis expression factors. In addition, the necroptosis inhibitor necrostatin-1 (Nec-1) was added to Dex(+)/hypoxia(+) and cultured for 12 h and 24 h. Then using an Apoptotic/Necrotic Cells Detection Kit the numbers of apoptotic and necrotic cells were counted and compared. In Dex(+)/hypoxia(+) group, expression of both RIP1 and RIP3 was found. Additionally, in Western blotting, the addition of Nec-1 attenuated their expression. A decrease in the number of cell deaths was also found following Nec-1 administration. Necroptosis has been implicated as a cause of death in osteocytic cell necrosis. Use of the necroptosis inhibitor, Nec-1, suggests a possible approach to preventing osteocytic cell necrosis even in an H-D stress environment when given within 12 h. |
| Databáze: | OpenAIRE |
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