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Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice
Jinlu Dai, … , Yinghua Qi, Evan T. Keller
Jinlu Dai, … , Yinghua Qi, Evan T. Keller
Published October 1, 2000
Citation Information: J Clin Invest. 2000;106(7):887-895. https://doi.org/10.1172/JCI10483.
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Article

Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice

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Abstract

To investigate the role of IL-6 in alcohol-mediated osteoporosis, we measured a variety of bone remodeling parameters in wild-type (il6+/+) or IL-6 gene knockout (il6–/–) mice that were fed either control or ethanol liquid diets for 4 months. In the il6+/+ mice, ethanol ingestion decreased bone mineral density, as determined by dual-energy densitometry; decreased cancellous bone volume and trabecular width and increased trabecular spacing and osteoclast surface, as determined by histomorphometry of the femur; increased urinary deoxypyridinolines, as determined by ELISA; and increased CFU-GM formation and osteoclastogenesis as determined ex vivo in bone marrow cell cultures. In contrast, ethanol ingestion did not alter any of these parameters in the il6–/– mice. Ethanol increased receptor activator of NF-κB ligand (RANKL) mRNA expression in the bone marrow of il6+/+ but not il6–/– mice. Additionally, ethanol decreased several osteoblastic parameters including osteoblast perimeter and osteoblast culture calcium retention in both il6+/+ and il6–/– mice. These findings demonstrate that ethanol induces bone loss through IL-6. Furthermore, they suggest that IL-6 achieves this effect by inducing RANKL and promoting CFU-GM formation and osteoclastogenesis.

Authors

Jinlu Dai, Dinlii Lin, Jian Zhang, Paula Habib, Peter Smith, Jill Murtha, Zheng Fu, Zhi Yao, Yinghua Qi, Evan T. Keller

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Figure 2

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Effect of ethanol ingestion on urinary deoxypyridinolines in wild-type o...
Effect of ethanol ingestion on urinary deoxypyridinolines in wild-type or IL-6 gene knockout mice. Il6+/+ or il6–/– mice were fed either a control diet or 5% ethanol diet for 4 months. The mice were then sacrificed, and urine was collected and evaluated for deoxypyridinolines (Dpd’s) and creatinine levels as described in Methods. Data are presented as mean (± SD) urinary Dpd corrected for creatinine levels. Data were analyzed using ANOVA and Fisher’s least significant difference for post hoc analysis. AP = 0.045 compared with control-fed il6+/+ mice. Measurements were performed in six to eight individual mice per group.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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