作者
Dong Min Kang,Kwon‐Ha Yoon,Ju‐Young Kim,Jae Min Oh,Myeungsu Lee,Sung Tae Jung,Seon Kwan Juhng,Young Hwan Lee
摘要
Rationale and Objectives To identify micro–computed tomography (CT) imaging biomarkers for evaluating the effects of emodin, a potential drug to treat osteoporosis, in the mouse model of lipopolysaccharide (LPS)-mediated osteoporosis. Materials and Methods Forty male imprinting control region (ICR) mice with LPS-induced bone resorption were equally divided into four experimental groups: phosphate-buffered saline–treated (control), emodin-treated, LPS-treated, and LPS + emodin–treated groups. Emodin (50 mg/kg) was administered orally on alternate days for 8 days, and LPS (5 mg/kg) was injected intraperitoneally on days 1 and 4. After 8 days, the mice were sacrificed, and micro-CT images of the left proximal femurs were obtained. Three-dimensional images were analyzed by using commercial software to measure the bone volume to total volume fraction (BV/TV), trabecular number (Tb-N), trabecular thickness (Tb-Th), and trabecular separation (Tb-Sp) as CT imaging biomarkers. Histologic analyses of the femurs were performed using hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP) immunohistochemical staining. Results The LPS + emodin–treated group demonstrated marked suppression of LPS-induced bone resorption compared to the LPS-treated group (BV/TV, 28.84% vs. 40.76%; Tb-N, 2.65 vs. 3.45 mm−1; Tb-Sp, 300.81 vs. 212.31 μm; Tb-Th, 116.94 vs. 131.25 μm). TRAP immunohistochemical analysis showed fewer osteoclasts per field of tissue in the LPS + emodin–treated group than in the LPS-treated group (27.8 vs. 41.8). The BV/TV, Tb-N, and Tb-Sp data correlated well with the histomorphometric findings. Conclusions The findings reveal a novel effect of emodin on bone remodeling in the LPS-mediated osteoporotic mouse model. The ex vivo micro-CT imaging is a promising tool for assessing the therapeutic effects of potential drugs on osteoporosis. To identify micro–computed tomography (CT) imaging biomarkers for evaluating the effects of emodin, a potential drug to treat osteoporosis, in the mouse model of lipopolysaccharide (LPS)-mediated osteoporosis. Forty male imprinting control region (ICR) mice with LPS-induced bone resorption were equally divided into four experimental groups: phosphate-buffered saline–treated (control), emodin-treated, LPS-treated, and LPS + emodin–treated groups. Emodin (50 mg/kg) was administered orally on alternate days for 8 days, and LPS (5 mg/kg) was injected intraperitoneally on days 1 and 4. After 8 days, the mice were sacrificed, and micro-CT images of the left proximal femurs were obtained. Three-dimensional images were analyzed by using commercial software to measure the bone volume to total volume fraction (BV/TV), trabecular number (Tb-N), trabecular thickness (Tb-Th), and trabecular separation (Tb-Sp) as CT imaging biomarkers. Histologic analyses of the femurs were performed using hematoxylin and eosin and tartrate-resistant acid phosphatase (TRAP) immunohistochemical staining. The LPS + emodin–treated group demonstrated marked suppression of LPS-induced bone resorption compared to the LPS-treated group (BV/TV, 28.84% vs. 40.76%; Tb-N, 2.65 vs. 3.45 mm−1; Tb-Sp, 300.81 vs. 212.31 μm; Tb-Th, 116.94 vs. 131.25 μm). TRAP immunohistochemical analysis showed fewer osteoclasts per field of tissue in the LPS + emodin–treated group than in the LPS-treated group (27.8 vs. 41.8). The BV/TV, Tb-N, and Tb-Sp data correlated well with the histomorphometric findings. The findings reveal a novel effect of emodin on bone remodeling in the LPS-mediated osteoporotic mouse model. The ex vivo micro-CT imaging is a promising tool for assessing the therapeutic effects of potential drugs on osteoporosis.