Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality
Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality
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DOI：
10.1016/j.bone.2013.07.003
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发表时间：
2013-10-01
期刊：
影响因子：
4.1
通讯作者：
Mabilleau, Guillaume
中科院分区：
文献类型：
--
作者：
Mieczkowska, Aleksandra;Irwin, Nigel;Mabilleau, Guillaume
骨是永久重塑的复杂网络的地方，激素和神经元因素，影响破骨细胞和成骨细胞的生物学。在这种情况下，胃肠道激素的作用已提出的证据表明，骨吸收显着下降福尔斯餐后。葡萄糖依赖性促胰岛素多肽（GIP）是一种候选激素，其受体葡萄糖依赖性促胰岛素多肽受体（GIPR）在骨中表达。在本研究中，我们研究了骨强度和质量的三点弯曲，定量X射线显微放射照相术，microCT，qBEI和FTIR在GIPR敲除（GIPR KO）小鼠模型，并与对照野生型（WT）动物进行比较。与WT动物相比，GIPR缺失动物的极限载荷（-11%）、刚度（-16%）、总吸收（-28%）和屈服后能量（-27%）显著降低。此外，尽管骨外径没有变化，但骨髓直径显著增加，因此GIPR缺陷动物的皮质厚度显著降低20%。在GIPR缺陷动物中，骨内膜表面的骨吸收显著增加，而骨形成不变。缺陷动物也表现出骨基质矿化程度的显著降低。此外，胶原基质的成熟交联的量在GIPR缺陷动物中显著减少，并且与降低的固有材料性质相关。总之，这些数据支持GIPR对骨强度和质量的积极影响。(C)2013 Elsevier Inc. All rights reserved.
Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. In this context, a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucose-dependent insulinotropic polypeptide (GIP) is one of the candidate hormones as its receptor, glucose-dependent insulinotropic polypeptide receptor (GIPR), is expressed in bone. In the present study we investigated bone strength and quality by three-point bending, quantitative x-ray microradiography, microCT, qBEI and FTIR in a GIPR knockout (GIPR KO) mouse model and compared with control wild-type (WT) animals. Animals with a deletion of the GIPR presented with a significant reduction in ultimate load (-11%), stiffness (-16%), total absorbed (-28%) and post-yield energies (-27%) as compared with WT animals. Furthermore, despite no change in bone outer diameter, the bone marrow diameter was significantly increased and as a result cortical thickness was significantly decreased by 20% in GIPR deficient animals. Bone resorption at the endosteal surface was significantly increased whilst bone formation was unchanged in GIPR deficient animals. Deficient animals also presented with a pronounced reduction in the degree of mineralization of bone matrix. Furthermore, the amount of mature cross-links of collagen matrix was significantly reduced in GIPR deficient animals and was associated with lowered intrinsic material properties. Taken together, these data support a positive effect of the GIPR on bone strength and quality. (C) 2013 Elsevier Inc. All rights reserved.