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

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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Effect of ethanol ingestion on osteoblast parameters in wild-type or IL-...
Effect of ethanol ingestion on osteoblast parameters 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 killed and bone marrow was collected from the femur. CFU-F, CFU-OB, and Ca. (a) To assess the marrow’s ability to support osteoblastogenesis, marrow cultures were maintained for 10 days in the presence of 50 μg/ml ascorbic acid and 10 mM β-glycerophosphate. CFU-Fs were determined by counting ALP-positive colonies as described in Methods. (b and c) To assess for the marrow’s ability to support osteoblast function, marrow cultures were maintained for 25 days in the presence of 50 μg/ml ascorbic acid and 10 mM β-glycerophosphate. (b) CFU-OBs were determined by counting von Kossa–positive colonies and (c) total calcium in the cultures was determined as described in Methods. Data are reported as mean (± SD). Data were analyzed using ANOVA and Fisher’s least significant difference for post hoc analysis. AP < 0.01 compared with control-fed il6–/– mice. BP = 0.02 compared with control-fed il6–/– mice. CP = 0.005 compared with control-fed il6–/– mice. Measurements were performed on ten individual mice per group.