Department of Food Science and Nutrition, Nara Women's University, Kita-uoya nishi-machi, Nara, Japan.
Int J Mol Med. 2010 Oct;26(4):611-8. doi: 10.3892/ijmm_00000506.
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.
胰岛素依赖型糖尿病（IDDM）与人类的骨质疏松/骨质疏松症风险增加有关。本研究使用链脲佐菌素（STZ）注射后 2 周的糖尿病大鼠来研究 IDDM 对成骨细胞和破骨细胞形成的影响。与对照组相比，糖尿病大鼠的胫骨和胫骨近端重量以及胫骨近端羟脯氨酸和钙含量显著降低。骨形成标志物碱性磷酸酶（ALP）活性和胫骨近端成骨细胞数量以及血清骨钙素水平显著降低。骨吸收标志物抗酒石酸酸性磷酸酶（TRAP）和组织蛋白酶 K 的活性以及胫骨近端破骨细胞数量和尿脱氧吡啶啉排泄量在糖尿病大鼠中更高。尽管受体激活核因子 kappaB（RANK）配体、骨保护素、巨噬细胞集落刺激因子和 c-fms 水平与对照值相似，但糖尿病大鼠的 RANK、c-fos、c-jun、TRAP 和组织蛋白酶 K 的 mRNA 水平均显著增加。糖尿病大鼠中 ALP、骨钙素和胶原 mRNA 的表达减少与 Runx2、Dlx5 和 osterix 的表达减少以及骨形成蛋白-2 的表达不变有关。糖尿病大鼠的 RANK 蛋白水平增加，Runx2 蛋白水平降低。胰岛素治疗可逆转 STZ 诱导的糖尿病大鼠骨中这些变化。这些结果表明，短期 IDDM 诱导破骨细胞形成增加，RANK 上调，成骨细胞形成减少，Runx2 下调。
