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

Abstract

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-kappaB (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.