Dysregulation of the ghrelin/RANKL/OPG pathway in bone mass is related to AIS osteopenia
Dysregulation of the ghrelin/RANKL/OPG pathway in bone mass is related to AIS osteopenia
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骨量中 ghrelin/RANKL/OPG 通路的失调与 AIS 骨质减少有关
DOI：
10.1016/j.bone.2020.115291
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发表时间：
2020-05-01
期刊：
影响因子：
4.1
通讯作者：
Liang, Zhuotao
中科院分区：
文献类型：
--
作者：
Xiao, Lige;Zhang, Hongqi;Liang, Zhuotao
背景资料：骨质减少在青少年特发性脊柱侧凸（AIS）中有很好的记录，ghrelin已被证明对骨代谢有积极的影响。然而，在AIS骨量减少的循环水平的ghrelin增加，和ghrelin和AIS骨量减少之间的关系尚不清楚。方法：共563 AIS和281年龄匹配的对照组被招募为这项研究。测量所有参与者的人体测量学和骨量。血浆ghrelin水平测定酶联免疫吸附试验（ELISA）在AIS和对照组。采用改进的多重连接检测反应分析单核苷酸多态性（SNPs）。收集小关节进行免疫组化，成骨基因和蛋白表达也进行了测量。结果：AIS骨量减少组体重指数明显低于对照组，而循环ghrelin明显高于对照组。AIS骨质减少组和对照组之间的四个ghrelin水平相关的SNPs没有显著差异。RNA和蛋白质分析显示AIS松质骨中RANKL/OPG较高，runx 2水平较低。与正常原代成骨细胞和BMSCs相比，AIS骨量减少原代细胞对相同的Ghrelin浓度梯度不敏感，成骨能力降低，OPG升高，RANKL.Conclusion：我们的结果表明，高循环Ghrelin水平可能不是AIS骨量减少基因变异的结果。Ghrelin/RANKL/OPG通路的失调可能导致成骨细胞和BMSCs的成骨能力降低，这可能与AIS骨量减少时骨量降低有关。
Background: Osteopenia has been well documented in adolescent idiopathic scoliosis (AIS), and ghrelin has been shown to have a positive effect on bone metabolism. However, the circulating level of ghrelin is increased in AIS osteopenia, and the relationship between ghrelin and low bone mass in AIS osteopenia remains unclear.Method: A total of 563 AIS and 281 age-matched controls were recruited for this study. Anthropometry and bone mass were measured in all participants. Plasma ghrelin levels were determined by enzyme-linked immunosorbent assay (ELISA) in both AIS and control groups. An improved multiplex ligation detection reaction was performed to analyze single-nucleotide polymorphisms (SNPs). Facet joints were collected and subjected to immunohistochemistry; osteogenic gene and protein expression was also measured. Furthermore, primary cells were extracted from facet joints and bone marrow to observe the response to ghrelin stimulation.Results: The body mass index was lower and circulating ghrelin was markedly higher in the AIS osteopenia group than in the control group. No significant difference was observed in four ghrelin level-related SNPs between the AIS osteopenia and control groups. RNA and protein analyses revealed higher RANKL/OPG and lower runx2 levels in AIS cancellous bone. Compared with normal primary osteoblasts and BMSCs, AIS osteopenia primary cells were insensitive to the same ghrelin concentration gradient and showed lower osteogenic ability, increases in OPG and decreases in RANKL.Conclusion: Our results indicate that high circulating ghrelin levels may not result from gene variations in AIS osteopenia. Dysregulation of the ghrelin/RANKL/OPG pathway may lead to decreased osteogenic ability of osteoblasts and BMSCs, which may be related to lower bone mass in AIS osteopenia.