Effects of osteoblast autophagy on glucocorticoid-induced femoral head necrosis
Ming Zhou1, Lei Liu2, Yaozeng Xu1, Jiannong Jiang2, Gang Liu3, Chenjun Zhai2
1Department of Orthopedics, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China
2Department of Orthopedics, Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu Province, People’s Republic of China
3Department of Orthopedics, Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, People’s Republic of China
Keywords: Autophagy, femoral head, glucocorticoid, necrosis, osteoblast
Abstract
Objectives: This study aims to explore the mechanism by which osteoblast autophagy participated in glucocorticoid-induced femoral head necrosis (FHN).
Materials and methods: Thirty male specific-pathogen-free C57 mice (age, one month; weighing 20-25 g) were randomly divided into blank control, dexamethasone and rapamycin-dexamethasone groups (n=10). After six weeks of intervention, right femoral head was obtained to observe morphology and to calculate percentage of empty lacunae. MC3T3-E1 cells were randomly divided into normal, dexamethasone, rapamycin and dexamethasone-rapamycin groups, and cultured for 24 h. Microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, mammalian target of rapamycin (mTOR) and Beclin-1 protein expressions were detected by Western blot.
Results: In rapamycin-dexamethasone group, some bone trabeculae in medullary cavity ruptured and atrophied, and subchondral bone underwent local necrosis. The total apoptosis rates of dexamethasone and rapamycin-dexamethasone groups surpassed that of blank control group, and the former two groups had significantly different rates (p<0.001). LC3-II/LC3-I of dexamethasone group was lower than those of rapamycin and dexamethasone-rapamycin groups (p<0.001), and the ratio of rapamycin group surpassed that of dexamethasone-rapamycin group (p<0.001). Dexamethasone group had higher mTOR protein expression than those of rapamycin and dexamethasone- rapamycin groups (p<0.001), and the expression of rapamycin group was lower than that of dexamethasone-rapamycin group (p<0.001). The Beclin-1 protein expression of dexamethasone group was lower than those of rapamycin and dexamethasone- rapamycin groups (p<0.001), and the expression of rapamycin group exceeded that of dexamethasone-rapamycin group (p<0.05).
Conclusion: Osteoblast autophagy may play a crucial protective role in dexamethasone-induced FHN. The attenuation of autophagy may be related to the affected expressions of key autophagy regulators mTOR and Beclin-1.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.