Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice.
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-kappaB 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.
Dai
J
J
Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Lin
D
D
Zhang
J
J
Habib
P
P
Smith
P
P
Murtha
J
J
Fu
Z
Z
Yao
Z
Z
Qi
Y
Y
Keller
E T
ET
D015502:Absorptiometry, Photon; D000437:Alcoholism / Q000150:complications*; D000818:Animals; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology*; D002454:Cell Differentiation; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000166:cytology*
D015850:Interleukin-6