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An Experimental Study of Steroid-induced Adipogenesis in Marrow Stromal Cells

LI Yueba

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Abstract

Objective To observe steroid-induced marrow stromal cell differentiation into adipocytes to elucidate the pathogenesis of the steroid-induced avascular necrosis of the femoral head. Methods The primary marrow stromal cells of the femur of the mouse were procured and cultured. The samples were isolated; after adherent growth culture in vitro, and were treated with dexamethasone which acted as adipocyte differ- entiation inducer. The cells in culture were stained with Sudan Ⅲ. The number of adipocytes were counted on a light microscope. Results After the cells in culture were treated with increasing(0, 1 × 10~-9, 1 × 10~-8, 1 × 10~-7, and 1 × 10~-6 mol/L) concentrations of dexamethasone for 21 days, the number of adipocytes, which was highest in 1 ×10~- 6 mol/L groups and lowest in the control, increased with higher concentrations of dexamethasone and showed a dose-dependent relation. Alkaline phosphatase activity in the cells exposed to higher concentration of dexamethasone(1 × 10~-7 mol/L) for 12 days was significantly lower than that in the control (P 0. 01 ). Conclusion Dexamethasone can directly induce marrow stromal cell differentiation into a large number of adipocytes and inhibit osteogenic differentiation. This might lead to an increase in marrow fat volume of the femoral head following administration of high dose of steroids; eventually an increase of intraosseous pressure occurred, with a decrease of vascular perfusion. Without sufficient repair of the necrotic bone, the final result is avascular necrosis of the femoral head.

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Objective To observe steroid-induced marrow stromal cell differentiation into adipocytes to elucidate the pathogenesis of the steroid-induced avascular necrosis of the femoral head. Methods The primary marrow stromal cells of the femur of the mouse were procured and cultured. The samples were isolated; after adherent growth culture in vitro, and were treated with dexamethasone which acted as adipocyte differ- entiation inducer. The cells in culture were stained with Sudan Ⅲ. The number of adipocytes were counted on a light microscope. Results After the cells in culture were treated with increasing(0, 1 × 10~-9, 1 × 10~-8, 1 × 10~-7, and 1 × 10~-6 mol/L) concentrations of dexamethasone for 21 days, the number of adipocytes, which was highest in 1 ×10~- 6 mol/L groups and lowest in the control, increased with higher concentrations of dexamethasone and showed a dose-dependent relation. Alkaline phosphatase activity in the cells exposed to higher concentration of dexamethasone(1 × 10~-7 mol/L) for 12 days was significantly lower than that in the control (P 0. 01 ). Conclusion Dexamethasone can directly induce marrow stromal cell differentiation into a large number of adipocytes and inhibit osteogenic differentiation. This might lead to an increase in marrow fat volume of the femoral head following administration of high dose of steroids; eventually an increase of intraosseous pressure occurred, with a decrease of vascular perfusion. Without sufficient repair of the necrotic bone, the final result is avascular necrosis of the femoral head.

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Available abstract

Objective To observe steroid-induced marrow stromal cell differentiation into adipocytes to elucidate the pathogenesis of the steroid-induced avascular necrosis of the femoral head. Methods The primary marrow stromal cells of the femur of the mouse were procured and cultured. The samples were isolated; after adherent growth culture in vitro, and were treated with dexamethasone which acted as adipocyte differ- entiation inducer. The cells in culture were stained with Sudan Ⅲ. The number of adipocytes were counted on a light microscope. Results After the cells in culture were treated with increasing(0, 1 × 10~-9, 1 × 10~-8, 1 × 10~-7, and 1 × 10~-6 mol/L) concentrations of dexamethasone for 21 days, the number of adipocytes, which was highest in 1 ×10~- 6 mol/L groups and lowest in the control, increased with higher concentrations of dexamethasone and showed a dose-dependent relation. Alkaline phosphatase activity in the cells exposed to higher concentration of dexamethasone(1 × 10~-7 mol/L) for 12 days was significantly lower than that in the control (P 0. 01 ). Conclusion Dexamethasone can directly induce marrow stromal cell differentiation into a large number of adipocytes and inhibit osteogenic differentiation. This might lead to an increase in marrow fat volume of the femoral head following administration of high dose of steroids; eventually an increase of intraosseous pressure occurred, with a decrease of vascular perfusion. Without sufficient repair of the necrotic bone, the final result is avascular necrosis of the femoral head.

Key concepts: Dexamethasone, Stromal cell, Bone marrow, Medicine, Adipocyte, Endocrinology, Adipogenesis, Internal medicine

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