High d(+)glucose concentration inhibits RANKL-induced osteoclastogenesis.
High d(+)glucose concentration inhibits RANKL-induced osteoclastogenesis.
复制标题
DOI：
10.1016/j.bone.2008.02.006
复制
发表时间：
2008-06
期刊：
影响因子：
4.1
通讯作者：
Y. Wittrant;Y. Gorin;K. Woodruff;D. Horn;H. Abboud;S. Mohan;S. Abboud‐Werner
中科院分区：
文献类型：
--
作者：
Y. Wittrant;Y. Gorin;K. Woodruff;D. Horn;H. Abboud;S. Mohan;S. Abboud‐Werner
糖尿病是一种与高血糖和骨代谢改变相关的慢性疾病，可导致并发症，包括骨质减少、骨折风险增加和骨质疏松症。高血糖与糖尿病性骨病的发病机制有关;然而，葡萄糖对破骨细胞生成的生物学效应尚不清楚。在本研究中，我们使用RAW 264.7细胞和骨髓巨噬细胞（BMM）作为模型，检查了高d（+）葡萄糖（d-Glc）和l（-）葡萄糖（l-Glc;渗透压控制）对RANKL诱导的破骨细胞生成的影响。将细胞暴露于持续的高葡萄糖水平以模拟糖尿病状况。采用抗酒石酸酸性磷酸酶（TRACP）试验分析破骨细胞形成，降钙素受体（CTR）和组织蛋白酶K mRNA的表达，并采用二氯二氢荧光素二乙酸酯（DCF-DA）荧光、caspase-3和核因子κ B（NF-κB）活性检查培养物的活性氧（ROS）。使用迁移试验评估细胞功能。结果首次表明，高d-Glc通过代谢途径抑制破骨细胞形成、ROS产生、caspase-3活性和对RANKL的迁移反应。我们的研究结果还表明，高d-Glc可能通过抗氧化机制抑制氧化还原敏感性NF-κB活性，从而改变RANKL诱导的破骨细胞形成。这项研究增加了我们对葡萄糖在糖尿病相关骨病中作用的理解。我们的数据表明，高葡萄糖水平可能会改变骨转换，通过减少破骨细胞分化和功能，在糖尿病和提供新的见解葡萄糖对破骨细胞的生物学效应。
Diabetes is a chronic disease associated with hyperglycemia and altered bone metabolism that may lead to complications including osteopenia, increased risk of fracture and osteoporosis. Hyperglycemia has been implicated in the pathogenesis of diabetic bone disease; however, the biologic effect of glucose on osteoclastogenesis is unclear. In the present study, we examined the effect of high d(+)glucose (d-Glc) and l(−)glucose (l-Glc; osmotic control) on RANKL-induced osteoclastogenesis using RAW264.7 cells and Bone Marrow Macrophages (BMM) as models. Cells were exposed to sustained high glucose levels to mimic diabetic conditions. Osteoclast formation was analyzed using tartrate resistant acid phosphatase (TRACP) assay, expression of calcitonin receptor (CTR) and cathepsin K mRNAs, and cultures were examined for reactive oxygen species (ROS) using dichlorodihydrofluorescein diacetate (DCF-DA) fluorescence, caspase-3 and Nuclear Factor kappaB (NF-κB) activity. Cellular function was assessed using a migration assay. Results show, for the first time, that high d-Glc inhibits osteoclast formation, ROS production, caspase-3 activity and migration in response to RANKL through a metabolic pathway. Our findings also suggest that high d-Glc may alter RANKL-induced osteoclast formation by inhibiting redox-sensitive NF-κB activity through an anti-oxidative mechanism. This study increases our understanding of the role of glucose in diabetes-associated bone disease. Our data suggest that high glucose levels may alter bone turnover by decreasing osteoclast differentiation and function in diabetes and provide new insight into the biologic effects of glucose on osteoclastogenesis.