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青少年特发性脊柱侧凸患者对瘦素的异常成骨反应。

Abnormal Osteoblastic Response to Leptin in Patients with Adolescent Idiopathic Scoliosis.

机构信息

SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong, SAR, China.

The Joint Scoliosis Research Center of the Chinese University of Hong Kong-Nanjing University, Hong Kong, SAR, China.

出版信息

Sci Rep. 2019 Nov 20;9(1):17128. doi: 10.1038/s41598-019-53757-3.

DOI:10.1038/s41598-019-53757-3
PMID:31748652
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6868007/
Abstract

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine with unknown etiology. Although leptin has been postulated as one of the etiologic factors in AIS, its effects on osteoblastic activity remain unknown. Herein, we conducted this study to investigate whether there are abnormal functional responses to leptin and abnormal expression of leptin receptor in AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 12 severe AIS girls and 6 non-AIS controls. The osteoblasts were exposed to different concentrations of leptin (0, 10, 100, 1000 ng/mL). The effects of leptin on cell proliferation, differentiation and mineralization were determined. Protein expressions of leptin receptor (LEP-R) under basal and osteogenic conditions were also evaluated by Western blot. Our results showed that leptin significantly stimulated osteoblasts from non-AIS subjects to proliferate, differentiate and mineralized. However, in the AIS group, the stimulatory effects of leptin on cell proliferation, differentiation, and mineralization were not observed. In addition, no statistically significant difference in the expression of leptin receptor under both basal and osteogenic conditions was found between AIS and control group. In conclusion, these findings might help to explain the low bone mass and deranged bone quality that is clinically associated with AIS girls.

摘要

青少年特发性脊柱侧凸(AIS)是一种脊柱的复杂三维结构畸形,病因不明。虽然瘦素被认为是 AIS 的病因之一,但它对成骨细胞活性的影响尚不清楚。在此,我们进行了这项研究,以调查 AIS 成骨细胞中是否存在瘦素的异常功能反应和瘦素受体的异常表达。通过体外实验,对 12 名严重 AIS 女孩和 6 名非 AIS 对照组的成骨细胞进行了分离。将成骨细胞暴露于不同浓度的瘦素(0、10、100、1000ng/ml)中。测定瘦素对细胞增殖、分化和矿化的影响。还通过 Western blot 评估基础和成骨条件下瘦素受体(LEP-R)的蛋白表达。结果显示,瘦素显著刺激非 AIS 组的成骨细胞增殖、分化和矿化。然而,在 AIS 组中,瘦素对细胞增殖、分化和矿化的刺激作用未观察到。此外,在基础和成骨条件下,AIS 组和对照组之间瘦素受体的表达无统计学差异。总之,这些发现可能有助于解释临床上与 AIS 女孩相关的低骨量和骨质量紊乱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c925/6868007/e21a3edb5f37/41598_2019_53757_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c925/6868007/02ed4542abb7/41598_2019_53757_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c925/6868007/9c16b7773f58/41598_2019_53757_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c925/6868007/e21a3edb5f37/41598_2019_53757_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c925/6868007/02ed4542abb7/41598_2019_53757_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c925/6868007/9c16b7773f58/41598_2019_53757_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c925/6868007/e21a3edb5f37/41598_2019_53757_Fig3_HTML.jpg

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本文引用的文献

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Sci Rep. 2016 Dec 19;6:39220. doi: 10.1038/srep39220.
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Adolescent idiopathic scoliosis.青少年特发性脊柱侧凸。
Nat Rev Dis Primers. 2015 Sep 24;1:15030. doi: 10.1038/nrdp.2015.30.
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骨转换标志物、瘦素与青少年特发性脊柱侧凸(AIS)女孩营养状况的关系。
Nutrients. 2020 Aug 31;12(9):2657. doi: 10.3390/nu12092657.
Spine (Phila Pa 1976). 2015 Oct 1;40(19):E1041-5. doi: 10.1097/BRS.0000000000001060.
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Association between components of body composition and scoliosis: a prospective cohort study reporting differences identifiable before the onset of scoliosis.身体成分各组成部分与脊柱侧弯之间的关联:一项前瞻性队列研究,报告脊柱侧弯发病前可识别的差异。
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Age-related changes of leptin and leptin receptor variants in healthy elderly and long-lived adults.
Geriatr Gerontol Int. 2015 Mar;15(3):365-71. doi: 10.1111/ggi.12267. Epub 2014 Feb 26.
6
Are volumetric bone mineral density and bone micro-architecture associated with leptin and soluble leptin receptor levels in adolescent idiopathic scoliosis?--A case-control study.青少年特发性脊柱侧弯患者的骨体积密度和骨微结构与瘦素及可溶性瘦素受体水平有关吗?——一项病例对照研究。
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7
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8
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