ECTS2014 Poster Presentations Cell biology: osteoblasts and bone formation (48 abstracts)
Reduced bone formation and increased adiposity with insulin resistance in interleukin-11 deficient mice
Bingzi Dong 1 , Takeshi Kondo 1 , Yukiyo Ohnishi 1 , Itsuro Endo 1 , Masahiro Abe 1 , Shinichi Aizawa 2 , Hiroshi Sakaue 3 & Toshio Matsumoto 1
1Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences, Tokushima, Japan; 2RIKEN Center for Developmental Biology, Kobe, Japan; 3Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
We previously reported that interleukin (IL)-11 plays an important role in the mechanical stress and PTH-induced stimulation of osteoblast differentiation and bone formation. Mechanical stress and PTH enhance IL-11 gene promoter activity and increase IL-11 expression. Increased IL-11 down-regulates dikkopf 1/2 (Dkk1/2) expression and stimulates canonical Wnt signaling, which enhances osteoblast differentiation. The present study was undertaken to clarify the physiological role of IL-11 in osteogenesis and adipogenesis by creating IL-11 deficient (IL-11KO) mice.
The growth curves of IL-11KO and WT mice were similar. Bone mineral density (BMD) measured by μCT revealed that lumbar and total femoral BMD was lower in IL-11KO mice compared with those in WT mice after 8 to 12 weeks of age. The reduction in BMD was observed at both cortical and cancellous bones in both male and female IL-11KO mice. Serum osteocalcin was lower in IL-11KO than in WT mice, while serum TRAP5b was similar in both groups. Bone histomorphometry revealed that Tb.Th, Ob.S/BS and N.Ob/BS were reduced in IL-11KO mice, but there was no significant difference in Oc.S/BS or N.Oc/BS between IL-11KO and WT mice. Immunohistochemical staining of sclerostin and SOST mRNA expression in the femur increased in IL-11KO mice compared with WT mice. Furthermore, adipose tissue mass, adipocyte number and size were increased with impaired glucose tolerance, higher fasting serum insulin level and higher HOMA-IR in IL-11KO mice compared with WT mice fed with high fat diet.
These observations are consistent with the notion that IL-11 plays an important physiological role in maintaining bone formation and bone mass without affecting bone resorption. In addition, the increased adiposity and insulin resistance observed in IL-11KO mice suggest the role of IL-11 in regulating energy metabolism, which may be mediated via its effect on canonical Wnt signaling.
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Bone Abstracts
ISSN 2052-1219 (online)
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