Effect and mechanisms of vitamin E on early steroid-induced avascular necrosis of femoral head in rats_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Mufan , ZHANG Eryang , Lü Leifeng , BAN Wenrui , DANG Xiaoqian ,  ZHANG Chen

The First Department of Orthopaedics, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an Shaanxi, 710004, P.R.China;

Corresponding?author：

ZHANG Chen, Email: osteozhang@163.com

Keywords：

Steroid-induced avascular necrosis of femoral head; vitamin E; apoptosis; rats

DOI：

10.7507/1002-1892.201801046

Video：

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Objective To investigate the possibility of mitochondria-dependent apoptosis as a mechanism of early steroid-induced avascular necrosis of femoral head (SANFH) in rats and vitamin E as a possible prevention strategy. Methods Seventy-two male Sprague Dawley rats were randomly divided into control group, model group, and intervention group, with 24 rats in each group. The rats in control group were not treated as normal control. The rats in model group and intervention group were established early SANFH models by lipopolysaccharide combined with methylprednisolone injection. At the same time, the rats in intervention group were injected with vitamin E (40 mg/kg) every day for 7 days. At 2, 4, and 8 weeks after the final injection, the bilateral femoral heads were harvested and observed by HE staining, TUNEL assay, immunohistochemical staining, and Western blot. The rate of empty lacunae, apoptotic index, and the expressions of Caspase-9, Caspase-3, and cytochrome-c (Cyt-c) proteins were calculated. Results According to histological staining, there were significant differences in the rate of empty lacunae between intervention group and control group at 8 weeks (P<0.05) and between intervention group and model group at 4 and 8 weeks (P<0.05). The apoptotic index of intervention group was significantly lower than that of model group at each time point (P<0.05). And there was significant difference between the intervention group and the control group at 8 weeks (P<0.05). According to immunohistochemistry staining and Western blot, the expressions of Cyt-c, Caspase-9, and Caspase-3 all significantly decreased in intervention group than those in model group at each time point (P<0.05); and the differences were significant between intervention group and control group at 8 weeks (P<0.05). Conclusion Vitamin E can delay the progression of early SANFH by reducing mitochondrial dependent osteocyte apoptosis.

Citation： LI Mufan, ZHANG Eryang, Lü Leifeng, BAN Wenrui, DANG Xiaoqian, ZHANG Chen. Effect and mechanisms of vitamin E on early steroid-induced avascular necrosis of femoral head in rats. Chinese Journal of Reparative and Reconstructive Surgery, 2018, 32(11): 1421-1428. doi: 10.7507/1002-1892.201801046 Copy

1.	譚鋼, 羅磊, 楊靜, 等. 3664 例全髖關節置換術相關危險因素分析. 中國矯形外科雜志, 2011, 19(17): 1431-1434.
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6.	Rojas E, Carlini RG, Clesca P, et al. The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling. Kidney Int, 2003, 63(5): 1915-1923.
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9.	Xu X, Wen H, Hu Y, et al. STAT1-caspase 3 pathway in the apoptotic process associated with steroid-induced necrosis of the femoral head. J Mol Histol, 2014, 45(4): 473-485.
10.	陳偉, 林映才, 馬現永, 等. 一些抗氧化劑的抗/促氧化作用及其機制. 動物營養學報, 2012, 24(4): 595-605.
11.	倉寶成, 宮璀璀, 王莉, 等. 維生素 E 在體內外具有抗氧化作用. 基礎醫學與臨床, 2016, 36(1): 80-84.
12.	Steinberg ME, Hayken GD, Steinberg DR. A quantitative system for staging avascular necrosis. J Bone Joint Surg (Br), 1995, 77(1): 34-41.
13.	Tsuji M, Ikeda H, Ishizu A, et al. Altered expression of apoptosis-related genes in osteocytes exposed to high-dose steroid hormones and hypoxic stress. Pathobiology, 2006, 73(6): 304-309.
14.	Zalavras C, Shah S, Birnbaum MJ, et al. Role of apoptosis in glucocorticoid-induced osteoporosis and osteonecrosis. Crit Rev Eukaryot Gene Expr, 2003, 13(2-4): 221-235.
15.	Kuribayashi M, Fujioka M, Takahashi KA, et al. Vitamin E prevents steroid-induced osteonecrosis in rabbits. Acta Orthop, 2010, 81(1): 154-160.
16.	Mikami T, Ichiseki T, Kaneuji A, et al. Prevention of steroid-induced osteonecrosis by intravenous administration of vitamin E in a rabbit model. J Orthop Sci, 2010, 15(5): 674-677.
17.	Ghosh A, Sil PC. A protein from Cajanus indicus Spreng protects liver and kidney against mercuric chloride-induced oxidative stress. Biol Pharm Bull, 2008, 31(9): 1651-1658.
18.	Ghosh A, Sil PC. Protection of acetaminophen induced mitochondrial dysfunctions and hepatic necrosis via Akt-NF-kappaB pathway: role of a novel plant protein. Chem Biol Interact, 2009, 177(2): 96-106.
19.	Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med, 2010, 48(6): 749-762.
20.	Rachek LI, Yuzefovych LV, Ledoux SP, et al. Troglitazone, but not rosiglitazone, damages mitochondrial DNA and induces mitochondrial dysfunction and cell death in human hepatocytes. Toxicol Appl Pharmacol, 2009, 240(3): 348-354.

1. 譚鋼, 羅磊, 楊靜, 等. 3664 例全髖關節置換術相關危險因素分析. 中國矯形外科雜志, 2011, 19(17): 1431-1434.
2. 馬劍雄, 何偉偉, 趙杰, 等. 股骨頭壞死發病機制研究的最新進展. 中國組織工程研究, 2017, 21(27): 4397-4402.
3. Sen RK. Management of avascular necrosis of femoral head at pre-collapse stage. Indian J Orthop, 2009, 43(1): 6-16.
4. O'Brien CA, Jia D, Plotkin LI, et al. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology, 2004, 145(4): 1835-1841.
5. Eberhardt AW, Yeager-Jones A, Blair HC. Regional trabecular bone matrix degeneration and osteocyte death in femora of glucocorticoid- treated rabbits. Endocrinology, 2001, 142(3): 1333-1340.
6. Rojas E, Carlini RG, Clesca P, et al. The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling. Kidney Int, 2003, 63(5): 1915-1923.
7. Mocetti P, Silvestrini G, Ballanti P, et al. Bcl-2 and Bax expression in cartilage and bone cells after high-dose corticosterone treatment in rats. Tissue Cell, 2001, 33(1): 1-7.
8. Liu Y, Porta A, Peng X, et al. Prevention of glucocorticoid-induced apoptosis in osteocytes and osteoblasts by calbindin-D28k. J Bone Miner Res, 2004, 19(3): 479-490.
9. Xu X, Wen H, Hu Y, et al. STAT1-caspase 3 pathway in the apoptotic process associated with steroid-induced necrosis of the femoral head. J Mol Histol, 2014, 45(4): 473-485.
10. 陳偉, 林映才, 馬現永, 等. 一些抗氧化劑的抗/促氧化作用及其機制. 動物營養學報, 2012, 24(4): 595-605.
11. 倉寶成, 宮璀璀, 王莉, 等. 維生素 E 在體內外具有抗氧化作用. 基礎醫學與臨床, 2016, 36(1): 80-84.
12. Steinberg ME, Hayken GD, Steinberg DR. A quantitative system for staging avascular necrosis. J Bone Joint Surg (Br), 1995, 77(1): 34-41.
13. Tsuji M, Ikeda H, Ishizu A, et al. Altered expression of apoptosis-related genes in osteocytes exposed to high-dose steroid hormones and hypoxic stress. Pathobiology, 2006, 73(6): 304-309.
14. Zalavras C, Shah S, Birnbaum MJ, et al. Role of apoptosis in glucocorticoid-induced osteoporosis and osteonecrosis. Crit Rev Eukaryot Gene Expr, 2003, 13(2-4): 221-235.
15. Kuribayashi M, Fujioka M, Takahashi KA, et al. Vitamin E prevents steroid-induced osteonecrosis in rabbits. Acta Orthop, 2010, 81(1): 154-160.
16. Mikami T, Ichiseki T, Kaneuji A, et al. Prevention of steroid-induced osteonecrosis by intravenous administration of vitamin E in a rabbit model. J Orthop Sci, 2010, 15(5): 674-677.
17. Ghosh A, Sil PC. A protein from Cajanus indicus Spreng protects liver and kidney against mercuric chloride-induced oxidative stress. Biol Pharm Bull, 2008, 31(9): 1651-1658.
18. Ghosh A, Sil PC. Protection of acetaminophen induced mitochondrial dysfunctions and hepatic necrosis via Akt-NF-kappaB pathway: role of a novel plant protein. Chem Biol Interact, 2009, 177(2): 96-106.
19. Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med, 2010, 48(6): 749-762.
20. Rachek LI, Yuzefovych LV, Ledoux SP, et al. Troglitazone, but not rosiglitazone, damages mitochondrial DNA and induces mitochondrial dysfunction and cell death in human hepatocytes. Toxicol Appl Pharmacol, 2009, 240(3): 348-354.

Chinese Journal of Reparative and Reconstructive Surgery

Effect and mechanisms of vitamin E on early steroid-induced avascular necrosis of femoral head in rats

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