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

AGEs(RAGE)受体对低周转骨的作用

• 批准号: 22790790
• 负责人: HAMADA Yasuhiro
• 金额: $ 2.58万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790790/
• 关键词: 糖尿病; 骨病変; 合併症; 糖化最終産物; 糖化最終産物受容体; 骨代謝; 酸化ストレス; 低回転骨

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.

我们曾报道糖尿病导致链脲佐菌素诱导的糖尿病小鼠骨转换率降低。已有研究表明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基因在骨代谢中的作用，我们利用RAGE基因敲除小鼠(RAGE-KO)研究了RAGE基因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)分别腹腔注射链脲佐菌素或赋形剂。将小鼠分为4组：1)非糖尿病WT组；2)非糖尿病RAGE-KO组；3)糖尿病WT组；4)糖尿病RAGE-KO组。在链脲佐菌素或赋形剂治疗12周后，评价股骨的物理性质和胫骨的静态和动态骨组织形态计量学参数。RAGE基因的缺失既不影响体重，也不影响血红蛋白A1c水平。RAGE缺失导致骨密度增加，这是因为在生理条件下破骨细胞功能降低，即不积累AGEs。相反，缺乏RAGE不影响糖尿病条件下骨代谢的改变，提示AGEs-RAGE相互作用可能不参与糖尿病骨减少的发病机制，尽管RAGE在骨代谢中起重要作用，但表现为骨转换低。

项目成果

The effects of the receptor for advanced glycation end products (RAGE) on bone metabolism under physiological and diabetic conditions

• DOI: 10.1007/s12020-010-9390-9
• 发表时间: 2010-12-01
• 期刊: ENDOCRINE
• 影响因子: 3.7
• 作者: Hamada, Yasuhiro;Kitazawa, Sohei;Fukagawa, Masafumi
• 通讯作者: Fukagawa, Masafumi

糖化最終産物(RAGE)の骨代謝における役割の解明

阐明晚期糖基化终末产物 (RAGE) 在骨代谢中的作用

• 发表时间: 2010
• 作者: Hamada Y;Kitazawa S;Kitazawa R;Kono K;Goto S;Komaba H;Fujii H;Yamamoto Y;Yamamoto H;Usami M;Fukagawa M.;Yasuhiro Hamada;濱田康弘;濱田康弘;濱田康弘;濱田康弘;濱田康弘
• 通讯作者: 濱田康弘

抗酸化ストレス作用が低回転骨病変に及ぼす効果の解明

阐明抗氧化应激对低旋转骨病变的影响

• 发表时间: 2011
• 作者: Hamada Y;Kitazawa S;Kitazawa R;Kono K;Goto S;Komaba H;Fujii H;Yamamoto Y;Yamamoto H;Usami M;Fukagawa M.;Yasuhiro Hamada;濱田康弘
• 通讯作者: 濱田康弘

Carvedilol Ameliorates Low-Turnover Bone Disease in Non-Obese Type 2 Diabetes

• DOI: 10.1159/000330853
• 发表时间: 2011-01-01
• 期刊: AMERICAN JOURNAL OF NEPHROLOGY
• 影响因子: 4.2
• 作者: Goto, Shunsuke;Fujii, Hideki;Fukagawa, Masafumi
• 通讯作者: Fukagawa, Masafumi

The effects of the receptor for advanced glycation end products (RAGE) on bone metabolism under physiological and diabetic conditio

生理及糖尿病状态下晚期糖基化终末产物受体（RAGE）对骨代谢的影响

• 发表时间: 2010
• 期刊: Endocrine
• 影响因子: 3.7
• 作者: Hamada Y;Kitazawa S;Kitazawa R;Kono K;Goto S;Komaba H;Fujii H;Yamamoto Y;Yamamoto H;Usami M;Fukagawa M.;Yasuhiro Hamada
• 通讯作者: Yasuhiro Hamada