Ding Ke-Hong, Wang Zai-Zhao, Hamrick Mark W, Deng Zhong-Bin, Zhou Li, Kang Baolin, Yan Sheng-Li, She Jin-Xiong, Stern David M, Isales Carlos M, Mi Qing-Sheng
Department of Medicine, Medical College of Georgia, Augusta, GA, USA.
Biochem Biophys Res Commun. 2006 Feb 24;340(4):1091-7. doi: 10.1016/j.bbrc.2005.12.107. Epub 2005 Dec 27.
The mechanisms underlying diabetes-mediated bone loss are not well defined. It has been reported that the advanced glycation endproducts (AGEs) and receptor for AGEs (RAGEs) are involved in diabetic complications. Here, mice deficient in RAGE were used as a model for investigating the effects of RAGE on bone mass. We found that RAGE-/- mice have a significantly increased bone mass and bone biomechanical strength and a decreased number of osteoclasts compared to wild-type mice. The serum levels of IL-6 and bone breakdown marker pyridinoline were significantly decreased in RAGE-/- mice. RAGE-/- mice maintain bone mass following ovariectomy, whereas wild-type mice lose bone mass. Furthermore, osteoclast-like cells do express RAGE mRNA. Our data therefore indicate that RAGE serves as a positive factor to regulate the osteoclast formation, directly implicates a role for RAGE in diabetes-promoted bone destruction, and documents that the AGE-RAGE interaction may account for diabetes associated bone loss.
糖尿病介导的骨质流失的潜在机制尚未完全明确。据报道，晚期糖基化终产物（AGEs）及其受体（RAGEs）参与了糖尿病并发症的发生。在此，以缺乏RAGE的小鼠作为模型，研究RAGE对骨量的影响。我们发现，与野生型小鼠相比，RAGE基因敲除小鼠的骨量和骨生物力学强度显著增加，破骨细胞数量减少。RAGE基因敲除小鼠血清中的IL-6水平和骨吸收标志物吡啶啉显著降低。RAGE基因敲除小鼠在卵巢切除术后能维持骨量，而野生型小鼠则会出现骨质流失。此外，破骨细胞样细胞确实表达RAGE mRNA。因此，我们的数据表明，RAGE作为一个正向因子调节破骨细胞的形成，直接表明RAGE在糖尿病促进的骨质破坏中发挥作用，并证明AGE-RAGE相互作用可能是糖尿病相关骨质流失的原因。
