Division of Nephrology and Kidney Center, Kobe University School of Medicine, Kobe, Japan.
Endocrine. 2010 Dec;38(3):369-76. doi: 10.1007/s12020-010-9390-9. Epub 2010 Oct 23.
It has been reported that AGEs and the receptor for AGEs (RAGEs) have been linked to the pathogenesis of diabetic microangiopathy. However, the relationship between RAGE and alteration in bone metabolism is unclear. Therefore, in order to determine the role of RAGE in bone metabolism, we investigated the effects of RAGE deletion on bone metabolism under physiological and diabetic conditions using RAGE knockout mice (RAGE-KO). Eight-week-old male RAGE-KO and wild-type littermates (WT) were intraperitoneally injected with either streptozotocin or vehicle. Mice were classified into four groups: (1) nondiabetic WT; (2) nondiabetic RAGE-KO; (3) diabetic WT; and (4) diabetic RAGE-KO. After 12 weeks of streptozotocin or vehicle treatment, the physical properties of femora and the static and dynamic parameters of bone histomorphometry of tibiae were assessed. The deletion of RAGE affected neither body weights nor hemoglobin A1c levels. RAGE deletion resulted in increased bone mineral density due to decreased osteoclast function under physiological conditions that is no accumulation of AGEs. In contrast, lacking RAGE did not affect the alteration in bone metabolism under diabetic conditions, suggesting that AGEs-RAGE interaction may not be involved in the pathogenesis of diabetic osteopenia, although RAGE plays a crucial role in bone metabolism.
已有报道称，糖基化终产物（AGEs）及其受体（RAGEs）与糖尿病微血管病变的发病机制有关。然而，RAGE 与骨代谢改变之间的关系尚不清楚。因此，为了确定 RAGE 在骨代谢中的作用，我们使用 RAGE 敲除小鼠（RAGE-KO）研究了 RAGE 缺失在生理和糖尿病条件下对骨代谢的影响。将 8 周龄雄性 RAGE-KO 和野生型同窝仔鼠（WT）经腹腔注射链脲佐菌素或载体。将小鼠分为四组：（1）非糖尿病 WT；（2）非糖尿病 RAGE-KO；（3）糖尿病 WT；和（4）糖尿病 RAGE-KO。链脲佐菌素或载体处理 12 周后，评估股骨的物理特性以及胫骨的静态和动态骨组织形态计量学参数。在生理条件下，由于破骨细胞功能下降导致 AGEs 无积累，RAGE 的缺失导致骨矿物质密度增加。相比之下，在糖尿病条件下，RAGE 的缺失并未影响骨代谢的改变，表明 AGEs-RAGE 相互作用可能与糖尿病性骨质疏松症的发病机制无关，尽管 RAGE 在骨代谢中起关键作用。
