首页 | 本学科首页   官方微博 | 高级检索  
检索        

Dexamethasone-induced adipogenesis in primary marrow stromal cell cultures: mechanism of steroid-induced osteonecrosis
作者姓名:Yin L  Li YB  Wang YS
作者单位:[1]Department of Orthopedics, First Affiliated Hospital of ZhengzhouUniversity, Zhengzhou 450052, China [2]Department of Biochemistry, Medical College of ZhengzhouUniversity, Zhengzhou 450052, China
摘    要:Background In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim of this study was to observe the effect of dexamethasone (Dex) on differentiation of marrow stromal cells (MSCs), and to investigate the pathobiological mechanism of steroid-induced osteonecrosis. Methods MSCs in cultures were treated with increasing concentrations of Dex (0, 10^-9, 10^-8, 10^-7, and 10^-6 mol/L) continuously for 21 days. The cells, which were exposed to 0 mol/L (control) or 10^-7 mol/L Dex for 4-21 days, were then cultured for 21 days without Dex. MSCs were stained with Sudan Ⅲ. Number of adipocytes was counted under a light microscope. The activity of alkaline phosphatase (ALP) of MSCs treated with 0, 10^-8, 10-7, and 10^-6 mol/L Dex for 12 days, and that treated with 0 mol/L and 10^-7 mol/L Dex for 8, 10, or 12 days were determined. The levels of triglycerides, osteocalcin and cell proliferation of MSCs treated with 0 mol/L and 10^-7 mol/L Dex were detected. The mRNA expression levels of adipose-specific 422(aP2) gene and osteogenic gene type I collagen in MSCs treated with 0 mol/L and 10^-7 mol/L Dex for 6 days were analyzed by whole-cell dot-blot hybridization. Statistical analysis was performed using Student's t test and analysis of variance. P values less than 0.05 were considered significant statistically. Results The number of adipocytes in cultures increased with the duration of MSCs' exposure to Dex and the concentration of Dex. The level of ALP activity in the MSCs decreased with concentration of Dex. In the control group, it was 8.69 times of that in the 10^-7 mol/L Dex group on day 12 (t=20.51, P〈0.001). The level of triglycerides in 10^-7 mol/L Dex group was 3.40 times of that in the control (t=11.00, P〈0.001). The levels of cell proliferation and osteocalcin in the control were 1.54 and 2.42 times of that in the 10^-7 mol/L Dex group respectively. As compared to the control, the mRNA expression of adipose-specific 422(aP2) gene in 10^-7mol/L Dex group was significantly increased (t=36.48, P〈0.001), and that of osteogenic gene type I collagen was decreased (t=42.07, P〈0.001). Conclusions Dex can directly induce the differentiation of MSCs into a large number of adipocytes and inhibit their osteogenic differentiation, which provide a novel explanation for the pathologic changes of steroid-induced osteonecrosis.

关 键 词:地塞米松  脂肪形成  骨髓干细胞  骨坏死
收稿时间:2005-04-18

Dexamethasone-induced adipogenesis in primary marrow stromal cell cultures: mechanism of steroid-induced osteonecrosis
Yin L,Li YB,Wang YS.Dexamethasone-induced adipogenesis in primary marrow stromal cell cultures: mechanism of steroid-induced osteonecrosis[J].Chinese Medical Journal,2006,119(7):581-588.
Authors:Yin Li  Li Yue-bai  Wang Yi-sheng
Institution:1. Department of Orthopedics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
2. Department of Biochemistry, Medical College of Zhengzhou University, Zhengzhou 450052, China
Abstract:BACKGROUND: In steroid-induced osteonecrosis, hypertrophy and hyperplasia of marrow fat cells and lipid deposition of osteocytes can be found in the femoral head. However, the precise reason is not clear yet. The aim of this study was to observe the effect of dexamethasone (Dex) on differentiation of marrow stromal cells (MSCs), and to investigate the pathobiological mechanism of steroid-induced osteonecrosis. METHODS: MSCs in cultures were treated with increasing concentrations of Dex (0, 10(-9), 10(-8), 10(-7), and 10(-6) mol/L) continuously for 21 days. The cells, which were exposed to 0 mol/L (control) or 10(-7) mol/L Dex for 4 - 21 days, were then cultured for 21 days without Dex. MSCs were stained with Sudan III. Number of adipocytes was counted under a light microscope. The activity of alkaline phosphatase (ALP) of MSCs treated with 0, 10(-8), 10(-7), and 10(-6) mol/L Dex for 12 days, and that treated with 0 mol/L and 10(-7) mol/L Dex for 8, 10, or 12 days were determined. The levels of triglycerides, osteocalcin and cell proliferation of MSCs treated with 0 mol/L and 10(-7) mol/L Dex were detected. The mRNA expression levels of adipose-specific 422 (aP2) gene and osteogenic gene type I collagen in MSCs treated with 0 mol/L and 10(-7) mol/L Dex for 6 days were analyzed by whole-cell dot-blot hybridization. Statistical analysis was performed using Student's t test and analysis of variance. P values less than 0.05 were considered significant statistically. RESULTS: The number of adipocytes in cultures increased with the duration of MSCs' exposure to Dex and the concentration of Dex. The level of ALP activity in the MSCs decreased with concentration of Dex. In the control group, it was 8.69 times of that in the 10(-7) mol/L Dex group on day 12 (t = 20.51, P < 0.001). The level of triglycerides in 10(-7) mol/L Dex group was 3.40 times of that in the control (t = 11.00, P < 0.001). The levels of cell proliferation and osteocalcin in the control were 1.54 and 2.42 times of that in the 10(-7) mol/L Dex group respectively. As compared to the control, the mRNA expression of adipose-specific 422 (aP2) gene in 10(-7) mol/L Dex group was significantly increased (t = 36.48, P < 0.001), and that of osteogenic gene type I collagen was decreased (t = 42.07, P < 0.001). CONCLUSIONS: Dex can directly induce the differentiation of MSCs into a large number of adipocytes and inhibit their osteogenic differentiation, which provide a novel explanation for the pathologic changes of steroid-induced osteonecrosis.
Keywords:Dexamethasone  bone marrow  adipocytes  osteonecrosis
本文献已被 CNKI 维普 万方数据 PubMed 等数据库收录!
点击此处可从《中华医学杂志(英文版)》浏览原始摘要信息
点击此处可从《中华医学杂志(英文版)》下载免费的PDF全文
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号