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褪黑素通过STIM1/ORAI1途径介导成骨细胞增殖。

Melatonin Mediates Osteoblast Proliferation Through the STIM1/ORAI1 Pathway.

作者信息

Cao Lili, Yang Keda, Yuan Wei, Zhou Siming, Zhao Rui, Qiu Shui

机构信息

Department of Medical Oncology, First Hospital of China Medical University, Shenyang, China.

Department of Orthopedics, First Hospital of China Medical University, Shenyang, China.

出版信息

Front Pharmacol. 2022 Mar 22;13:851663. doi: 10.3389/fphar.2022.851663. eCollection 2022.

DOI:10.3389/fphar.2022.851663
PMID:35392575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8980543/
Abstract

Based on the positive correlation between bone mineral density and melatonin levels in blood, this study confirmed that melatonin supplementation prevents postmenopausal osteoporosis. We further confirmed that melatonin promotes an increase in intracellular calcium concentrations through the STIM1/ORAI1 pathway, thereby inducing the proliferation of osteoblasts. Osteoporosis (OP) is a progressive, systemic bone disease that is one of the main causes of disability and death in elderly female patients. As an amine hormone produced by the human pineal gland, melatonin plays an important role in regulating bone metabolism. This study intends to investigate the relationship between melatonin levels in human blood and bone density and to suggest the efficacy of melatonin in treating osteoporosis by performing and experiments. We used liquid chromatography-tandem mass spectrometry to determine the serum melatonin levels in postmenopausal women with osteoporosis and young women with a normal bone mass. The bone density, BV/TV, Tb.Th, Tb.Sp and other indicators of postmenopausal osteoporosis and mice with a normal bone mass were detected by measuring bone density and micro-CT. The intracellular calcium ion concentration was detected using fluorescence microscopy and a full-wavelength multifunctional microplate reader, and the expression of SOCE-related genes and STIM1/ORAI1 proteins was detected using PCR and WB. This study confirmed that bone density positively correlates with the melatonin level in human blood. In the animal model, melatonin supplementation reverses postmenopausal osteoporosis. We explored the internal mechanism of melatonin treatment of osteoporosis. Melatonin promotes an increase in intracellular calcium ion concentrations through the STIM1/ORAI1 pathway to induce osteoblast proliferation. This study provides an important theoretical basis for the clinical application of melatonin in patients with osteoporosis and helps to optimize the diagnosis and treatment of postmenopausal osteoporosis.

摘要

基于骨密度与血液中褪黑素水平之间的正相关关系,本研究证实补充褪黑素可预防绝经后骨质疏松症。我们进一步证实,褪黑素通过STIM1/ORAI1途径促进细胞内钙浓度升高,从而诱导成骨细胞增殖。骨质疏松症(OP)是一种进行性全身性骨病,是老年女性患者致残和死亡的主要原因之一。褪黑素作为人体松果体产生的一种胺类激素,在调节骨代谢中起重要作用。本研究旨在通过进行[具体实验]和[具体实验],探讨人体血液中褪黑素水平与骨密度之间的关系,并提示褪黑素治疗骨质疏松症的疗效。我们使用液相色谱-串联质谱法测定骨质疏松症绝经后女性和骨量正常的年轻女性的血清褪黑素水平。通过测量骨密度和显微CT检测绝经后骨质疏松症患者和骨量正常小鼠的骨密度、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁间距(Tb.Sp)等指标。使用荧光显微镜和全波长多功能微孔板读数器检测细胞内钙离子浓度,使用PCR和WB检测SOCE相关基因和STIM1/ORAI1蛋白的表达。本研究证实骨密度与人体血液中褪黑素水平呈正相关。在动物模型中,补充褪黑素可逆转绝经后骨质疏松症。我们探索了褪黑素治疗骨质疏松症的内在机制。褪黑素通过STIM1/ORAI1途径促进细胞内钙离子浓度升高,以诱导成骨细胞增殖。本研究为褪黑素在骨质疏松症患者中的临床应用提供了重要的理论依据,并有助于优化绝经后骨质疏松症的诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/cd0b59872f99/fphar-13-851663-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/a8a3251b1229/fphar-13-851663-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/67f4157abb00/fphar-13-851663-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/e084cb70b852/fphar-13-851663-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/cd0b59872f99/fphar-13-851663-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/a8a3251b1229/fphar-13-851663-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/67f4157abb00/fphar-13-851663-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/e084cb70b852/fphar-13-851663-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56ba/8980543/cd0b59872f99/fphar-13-851663-g004.jpg

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Life Sci. 2020 Sep 15;257:118044. doi: 10.1016/j.lfs.2020.118044. Epub 2020 Jul 2.
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Determinants of imminent fracture risk in postmenopausal women with osteoporosis.
Front Pharmacol. 2022 Oct 7;13:975181. doi: 10.3389/fphar.2022.975181. eCollection 2022.
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Osteoporos Int. 2020 Nov;31(11):2103-2111. doi: 10.1007/s00198-020-05294-3. Epub 2020 Jul 1.
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