Int J Med Sci 2018; 15(3):205-209. doi:10.7150/ijms.22525 This issue

Research Paper

Mitochondrial stress and redox failure in steroid-associated osteonecrosis

Masanobu Tsuchiya1, Toru Ichiseki1✉, Shusuke Ueda1, Yoshimichi Ueda2, Miyako Shimazaki2, Ayumi Kaneuji1, Norio Kawahara1

1. Department of Orthopaedic Surgery,Kanazawa Medical University, Daigaku 1-1,Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan
2. Department of Pathology, Kanazawa Medical University, Daigaku 1-1, Uchinada, Kahoku-gun, Ishikawa, 920-0293, Japan

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Tsuchiya M, Ichiseki T, Ueda S, Ueda Y, Shimazaki M, Kaneuji A, Kawahara N. Mitochondrial stress and redox failure in steroid-associated osteonecrosis. Int J Med Sci 2018; 15(3):205-209. doi:10.7150/ijms.22525. Available from

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The purpose of the role of antioxidant enzymes and mitochondria in the developmental mechanism of steroid-associated osteonecrosis in the femur. In the present study Japanese white rabbits (mean weight 3.5kg) were injected into the gluteus with methylprednisolone (MP) 20mg/kg, and killed after 3 days (MP3 group), 5 days (MP5 group), and 14 days (MP14 group) (n=3 each). As a Control group (C group) Japanese white rabbits not administered MP were used. In experiment 1, the expression of the antioxidant enzymes Superoxide dismutade (SOD) and catalase was compared in liver, kidney, heart, humerus, and femur in C group, and the presence/absence of mitochondria transcription factor A (TFAM) expression was determined by Western blotting (WB) and used to evaluate the number of mitochondria and their function. In experiment 2, the presence/absence of necrosis was determined by immunohistochemistry, while changes in the expression of SOD, catalase, and TFAM in the femur after steroid administration were determined by Western blotting (WB). In experiment 1, intense expression of all of SOD, catalase, and TFAM was found in the liver, kidney, and heart as compared to the humerus and femur. In experiment 2, the expression of all of SOD, catalase, and TFAM in MP3 and MP5 groups was decreased on WB as compared with C group, while in MP14 group a tendency to improvement was seen. Accordingly, steroid-associated mitochondrial injury and redox failure are concluded to be important elements implicated in the pathogenesis of osteonecrosis.

Keywords: transcription factor A (TFAM), Superoxide dismutase (SOD), catalase, steroid-associated osteonecrosis, redox