Interleukin-11 as a stimulatory factor for bone formation prevents bone loss with advancing age in mice.
Cytokines in interleukin (IL)-11 subfamily participate in the regulation of bone cell proliferation and differentiation. We report here positive effects of IL-11 on osteoblasts and bone formation. Overexpression of human IL-11 gene in transgenic mice resulted in the stimulation of bone formation to increase cortical thickness and strength of long bones, and in the prevention of cortical bone loss with advancing age. Bone resorption and osteoclastogenesis were not affected in IL-11 transgenic mice. In experiments in vitro, IL-11 stimulated transcription of the target gene for bone morphogenetic protein (BMP) via STAT3, leading to osteoblastic differentiation in the presence of BMP-2, but inhibited adipogenesis in bone marrow stromal cells. These results indicate that IL-11 is a stimulatory factor for osteoblastogenesis and bone formation to conserve cortical bone, possibly by enhancing BMP actions in bone. IL-11 may be a new therapeutic target for senile osteoporosis.
Takeuchi
Yasuhiro
Y
Division of Endocrinology and Nephrology, Department of Medicine, University of Tokyo School of Medicine, Japan. takeuchi-tky@umin.ac.jp
Watanabe
Sumiyo
S
Ishii
Genichiro
G
Takeda
Shu
S
Nakayama
Konosuke
K
Fukumoto
Seiji
S
Kaneta
Yasuyuki
Y
Inoue
Daisuke
D
Matsumoto
Toshio
T
Harigaya
Kenichi
K
Fujita
Toshiro
T
D000375:Aging / Q000473:pathology*; D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D001862:Bone Resorption / Q000517:prevention & control*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D017931:DNA Primers; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014158:Transcription, Genetic / Q000187:drug effects; D000077288:Troglitazone
D019485:Bone Morphogenetic Proteins; D002839:Chromans; D017931:DNA Primers; D017370:Interleukin-11; D011994:Recombinant Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone