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新橘皮苷通过抑制长链非编码 RNA HOTAIR 的组蛋白修饰改善激素诱导的股骨头坏死。

Neohesperidin Ameliorates Steroid-Induced Osteonecrosis of the Femoral Head by Inhibiting the Histone Modification of lncRNA HOTAIR.

机构信息

Department of Joint Surgery and Sports Medicine, Changzheng Hospital, Naval Medical University, Shanghai, People's Republic of China.

出版信息

Drug Des Devel Ther. 2020 Dec 7;14:5419-5430. doi: 10.2147/DDDT.S255276. eCollection 2020.

DOI:10.2147/DDDT.S255276
PMID:33324039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7733036/
Abstract

BACKGROUND: Neohesperidin (NH) and lncRNA HOTAIR (HOTAIR) could regulate osteoclastic and osteogenic differentiation. This study aimed to explore whether HOTAIR-mediated osteogenic differentiation was regulated by NH. METHODS: Steroid-induced osteonecrosis of the femoral head (SONFH) mice model was established. Histopathological changes in mouse osteonecrosis tissues were detected by hematoxylin-eosin staining. Bone marrow stromal cells (BMSCs) were isolated from healthy mice bone marrow samples by Ficoll density gradient and identified by flow cytometry. After treating the BMSCs with NH and dexamethasone or transfecting with HOTAIR overexpression plasmids and siHOTAIR, histone modification of HOTAIR, the cell viability, osteogenic differentiation, and adipogenic differentiation were detected by chromatin immunoprecipitation, MTT, Alizarin Red and Oil Red O staining, respectively. The expressions of HOTAIR and differentiation-related factors in the BMSCs were detected by RT-qPCR and Western blot. RESULTS: HOTAIR was highly expressed in SONFH model mice. NH ameliorated histopathological changes in the model mice, but the effect was reversed by overexpressed HOTAIR. NH increased viability of BMSCs and the H3K27me3 occupancy of HOTAIR, but decreased the expression and the H3K4me3 occupancy of HOTAIR. HOTAIR expression was down-regulated in BMSCs after osteogenic differentiation but was up-regulated after adipogenic differentiation. HOTAIR overexpression inhibited osteogenic differentiation and the expressions of RUNX2, OCN, and ALP, but increased adipogenic differentiation and the expressions of LPL and PPARr in BMSCs; moreover, the opposite results were observed in siHOTAIR. CONCLUSION: NH ameliorated SONFH by inhibiting the histone modifications of HOTAIR.

摘要

背景：新橙皮苷（NH）和长链非编码 RNA HOTAIR（HOTAIR）可调节破骨细胞和成骨细胞分化。本研究旨在探讨 HOTAIR 是否通过 NH 调节成骨细胞分化。

方法：建立激素诱导性股骨头坏死（SONFH）小鼠模型。通过苏木精-伊红染色检测小鼠骨坏死组织的组织病理学变化。采用 Ficoll 密度梯度法从健康小鼠骨髓样本中分离骨髓基质细胞（BMSCs），并通过流式细胞术进行鉴定。用 NH 和地塞米松处理 BMSCs，或转染 HOTAIR 过表达质粒和 siHOTAIR 后，通过染色质免疫沉淀、MTT、茜素红和油红 O 染色分别检测 HOTAIR 的组蛋白修饰、细胞活力、成骨分化和脂肪分化。通过 RT-qPCR 和 Western blot 检测 BMSCs 中 HOTAIR 和分化相关因子的表达。

结果：HOTAIR 在 SONFH 模型小鼠中高表达。NH 改善了模型小鼠的组织病理学变化，但过表达的 HOTAIR 则逆转了这一作用。NH 增加了 BMSCs 的活力和 HOTAIR 的 H3K27me3 占有率，但降低了 HOTAIR 的表达和 H3K4me3 占有率。HOTAIR 在 BMSCs 成骨分化后表达下调，但在脂肪分化后表达上调。HOTAIR 过表达抑制了 BMSCs 的成骨分化和 RUNX2、OCN 和 ALP 的表达，但增加了 BMSCs 的脂肪分化和 LPL 和 PPARγ的表达；相反，siHOTAIR 则产生了相反的结果。

结论：NH 通过抑制 HOTAIR 的组蛋白修饰改善了 SONFH。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/73f25b2b4244/DDDT-14-5419-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/954e18ac8f24/DDDT-14-5419-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/3b3945cb5707/DDDT-14-5419-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/fd911169333e/DDDT-14-5419-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/787e00fe2750/DDDT-14-5419-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/73f25b2b4244/DDDT-14-5419-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/954e18ac8f24/DDDT-14-5419-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/3b3945cb5707/DDDT-14-5419-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/fd911169333e/DDDT-14-5419-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/787e00fe2750/DDDT-14-5419-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82e/7733036/73f25b2b4244/DDDT-14-5419-g0005.jpg

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[1]
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Front Genet. 2025-6-4

[2]
Recent advances in osteonecrosis of the femoral head: a focus on mesenchymal stem cells and adipocytes.

J Transl Med. 2025-5-27

[3]
A HOTAIR-associated super-enhancer orchestrates glioblastoma malignancy via MEST.

Oncogenesis. 2025-4-7

[4]
Silence of HOTAIR promotes osteogenic differentiation and accelerates distraction osteogenesis by mediating FTO ubiquitination.

J Orthop Translat. 2025-1-20

[5]
Mitigation of BMP-induced inflammation in craniofacial bone regeneration and improvement of bone parameters by dietary hesperidin.

Sci Rep. 2024-1-31

[6]
Insight into Steroid-Induced ONFH: The Molecular Mechanism and Function of Epigenetic Modification in Mesenchymal Stem Cells.

Biomolecules. 2023-12-20

[7]
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J Orthop Surg Res. 2023-11-14

[8]
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[9]
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[10]
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本文引用的文献

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Polydatin promotes the osteogenic differentiation of human bone mesenchymal stem cells by activating the BMP2-Wnt/β-catenin signaling pathway.

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