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Increased expression of the receptor for activation of NF-κB and decreased runt-related transcription factor 2 expression in bone of rats with streptozotocin-induced diabetes

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Insulin-dependent diabetes mellitus (IDDM) is associated with an increased risk of osteopenia/osteoporosis in humans. The effects of IDDM on osteoblastogenesis and osteoclastogenesis were investigated using diabetic rats at 2 weeks after the streptozotocin (STZ) injection. The weight of the tibia and proximal tibia and the amount of hydroxyproline and calcium in the proximal tibia were significantly lower in diabetic rats than control rats. Markers of bone formation, alkaline phosphatase (ALP) activity and the number of osteoblasts in the proximal tibia and the serum osteocalcin level, were significantly lower. Markers of bone resorption, activity of tartrate-resistant acid phosphatase (TRAP) and cathepsin K and the number of osteoclasts in the proximal tibia and urinary excretion of deoxypyridinoline, were higher in diabetic rats than control rats. mRNA levels of receptor for activation of NF-κB (RANK), c-fos, c-jun, TRAP and cathepsin K were significantly increased in diabetic rats, although RANK ligand, osteoprotegerin, macrophage colony-stimulating factor and c-fms levels were similar to the control value. The decreased expression of ALP, osteoclacin and collagen mRNA in diabetic rats was associated with decreases in the expression of Runx2, Dlx5 and osterix and an unaltered expression of bone morphogenic protein-2. The level of RANK protein increased and Runx2 protein decreased in diabetic rats. These changes in the bone of STZ-induced diabetic rats were reversed by insulin-treatment. These suggested that short-term IDDM induced upregulation of osteoclastogenesis with an increase in RANK and downregulation of osteoblastogenesis with a decrease in Runx2 in bone.
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Document Type: Research Article

Affiliations: Department of Food Science and Nutrition, Nara Women's University, Kita-uoya nishi-machi, Nara 630-8506, Japan

Publication date: October 1, 2010

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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