The Role of Receptor for AGEs(RAGE) on Low Turnover Bone

我们已经报道了糖尿病在链脲佐菌素诱导的糖尿病小鼠中诱导低周转率骨。据报道，AGEs及其受体（RAGE）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缺失对生理和糖尿病条件下骨代谢的影响。8周龄雄性RAGE-KO和野生型窝仔（WT）腹腔注射链脲佐菌素或载药。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；4)糖尿病RAGE-KO。链脲佐菌素或载药治疗12周后，观察大鼠股骨的物理特性及胫骨骨组织形态学的静态和动态参数。RAGE的缺失既不影响体重，也不影响血红蛋白A1c水平。在没有AGEs积累的生理条件下，RAGE缺失导致破骨细胞功能下降，从而导致骨密度增加。相比之下，缺乏RAGE并不影响糖尿病条件下骨代谢的改变，这表明尽管RAGE在骨代谢中起重要作用，但age -RAGE相互作用可能不参与糖尿病性骨质减少的发病机制，糖尿病性骨质减少表现为低转换骨。

We have reported that diabetes induced low turnover bone in streptozotocin-induced diabetic mouse. It has been reported that AGEs and the receptor for AGEs(RAGE) 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 divided 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, which expresses low turnover bone, although RAGE plays an important role in bone metabolism.