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通过抑制肾上腺髓质素预防绝经后骨质疏松症模型中的骨质流失

Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition.

作者信息

Martínez-Herrero Sonia, Larrayoz Ignacio M, Ochoa-Callejero Laura, Fernández Luis J, Allueva Alexis, Ochoa Ignacio, Martínez Alfredo

机构信息

Angiogenesis Interest Group, Oncology Area, Center for Biomedical Research of La Rioja, Fundación Rioja Salud Logroño, Spain.

Centro de Investigación Biomédica en Red, Aragon Institute of Health SciencesZaragoza, Spain; Group of Structural Mechanics and Materials Modelling, Aragón Institute of Engineering Research (I3A), University of ZaragozaZaragoza, Spain.

出版信息

Front Physiol. 2016 Jun 30;7:280. doi: 10.3389/fphys.2016.00280. eCollection 2016.

DOI:10.3389/fphys.2016.00280
PMID:27445864
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4928306/
Abstract

Despite recent advances in the understanding and treatment options for osteoporosis, this condition remains a serious public health issue. Adrenomedullin (AM) is a regulatory peptide with reported activity on bone remodeling. To better understand this relationship we built an inducible knockout for AM. An outstanding feature of knockout mice is their heavier weight due, in part, to the presence of denser bones. The femur of knockout animals was denser, had more trabeculae, and a thicker growth plate than wild type littermates. The endocrine influence of AM on bone seems to be elicited through an indirect mechanism involving, at least, the regulation of insulin, glucose, ghrelin, and calcitonin gene-related peptide (CGRP). To confirm the data we performed a pharmacological approach using the AM inhibitor 16311 in a mouse model of osteoporosis. Ovariectomized females showed significant bone mass loss, whereas ovariectomized females treated with 16311 had similar bone density to sham operated females. In conclusion, we propose the use of AM inhibitors for the treatment of osteoporosis and other conditions leading to the loss of bone mass.

摘要

尽管在骨质疏松症的认识和治疗选择方面最近取得了进展，但这种疾病仍然是一个严重的公共卫生问题。肾上腺髓质素（AM）是一种调节肽，据报道对骨重塑有活性。为了更好地理解这种关系，我们构建了AM的诱导性敲除模型。敲除小鼠的一个显著特征是它们体重更重，部分原因是骨骼更致密。与野生型同窝小鼠相比，敲除动物的股骨更致密，小梁更多，生长板更厚。AM对骨骼的内分泌影响似乎是通过一种间接机制引发的，至少涉及胰岛素、葡萄糖、胃饥饿素和降钙素基因相关肽（CGRP）的调节。为了证实这些数据，我们在骨质疏松症小鼠模型中使用AM抑制剂16311进行了药理学研究。去卵巢雌性小鼠出现了显著的骨量丢失，而用16311治疗的去卵巢雌性小鼠的骨密度与假手术雌性小鼠相似。总之，我们建议使用AM抑制剂来治疗骨质疏松症和其他导致骨量丢失的疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/aae81c1cf33a/fphys-07-00280-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/3b3532fee9c6/fphys-07-00280-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/ee137b24e697/fphys-07-00280-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/165968e6e013/fphys-07-00280-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/aae81c1cf33a/fphys-07-00280-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/3b3532fee9c6/fphys-07-00280-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/1ea1d70a50cd/fphys-07-00280-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/413f12b008d6/fphys-07-00280-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/ee137b24e697/fphys-07-00280-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/165968e6e013/fphys-07-00280-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622f/4928306/aae81c1cf33a/fphys-07-00280-g0006.jpg

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