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Exp Ther Med. 2017 Jul;14(1):367-372. doi: 10.3892/etm.2017.4508. Epub 2017 May 23.

Overactivated autophagy contributes to steroid-induced avascular necrosis of the femoral head.

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1
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Abstract

Steroid-induced avascular necrosis of the femoral head (SANFH) is a mainly bilateral complication of steroid therapy that involves extensive necrosis, and frequently occurs in young and middle-aged individuals, with a high disability rate. Autophagy is an intracellular lysosomal degradation process occurring in numerous diseases. However, the effect of dexamethasone (DXM)-induced autophagy on osteoblasts is unclear. The aim of the present study was to investigate the effects of autophagy on SANFH. In the present study, femoral head of SANFH patients was collected, and the autophagy in the samples was evaluated. In addition, cell proliferation, membrane integrity and differentiation of osteoblasts were also detected to confirm the effect of DXM on a mouse osteoblasts cell MC3T3-E1 in vitro. Beclin 1 and microtubule-associated protein 1 light chain 3 were used as the markers of autophagy, while the autophagy inhibitor 3-methyladenine (3-MA) was used to investigate the role of autophagy in DXM-challenged osteoblasts. Immunohistochemistry results demonstrated that Beclin1 was markedly increased in the femoral head of SANFH patients. Furthermore, the treatment of osteoblasts with DXM decreased cell viability, increased lactate dehydrogenase activity in the cell culture supernatant, and reduced the alkaline phosphatase activity and bone morphogenetic protein-2 expression in osteoblasts in vitro. By contrast, 3-MA treatment attenuated the cell injury induced by DXM. The present study indicates that overactivated autophagy may be an important factor contributing to SANFH, and autophagy may be a potential target for the prevention of SANFH.

KEYWORDS:

autophagy; dexamethasone; osteoblast; steroid-induced avascular necrosis of the femoral head

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