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[微小RNA介导的PPARγ相关信号通路在激素性股骨头坏死脂质代谢中的作用研究进展]

[Research progress on the effect of miRNA-mediated PPARγ-related signaling pathways on lipid metabolism in steroid-induced osteonecrosis of femoral head].

作者信息

Gao Hai-Yuan, Wang Xiao-Ping, Zhou Ming-Wang, Yang Xing, He Bang-Jing

机构信息

School of Clinical Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China.

Translational Medicine Research Center, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China.

出版信息

Sheng Li Xue Bao. 2025 Jun 25;77(3):493-503. doi: 10.13294/j.aps.2025.0044.

DOI:10.13294/j.aps.2025.0044
PMID:40566716
Abstract

Steroid-induced osteonecrosis of femoral head (SONFH) is a disease characterized by femoral head collapse and local pain caused by excessive use of glucocorticoids. Peroxisome proliferator-activated receptor-γ (PPARγ) is mainly expressed in adipose tissue. Wnt/β-catenin, AMPK and other related signaling pathways play an important role in regulating adipocyte differentiation, fatty acid uptake and storage. Bone marrow mesenchymal cells (BMSCs) have the ability to differentiate into adipocytes or osteoblasts, and the use of hormones upregulates PPARγ expression, resulting in BMSCs biased towards adipogenic differentiation. The increase of adipocytes affects the blood supply and metabolism of the femoral head, and the decrease of osteoblasts leads to the loss of trabecular bone, which eventually leads to partial or total ischemic necrosis and collapse of the femoral head. MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate gene expression by inhibiting the transcription or translation of target genes, thereby affecting cell function and disease progression. Studies have shown that miRNAs affect the progression of SONFH by regulating PPARγ lipid metabolism-related signaling pathways. Therefore, it may be an accurate and feasible SONFH treatment strategy to regulate adipogenic-osteoblast differentiation in BMSCs by targeted intervention of miRNA differential expression to improve lipid metabolism. In this paper, the miRNA-mediated PPARγ-related signaling pathways were classified and summarized to clarify their effects on lipid metabolism in SONFH, providing a theoretical reference for miRNA targeted therapy of SONFH, and then providing scientific evidence for SONFH precision medicine.

摘要

类固醇诱导的股骨头坏死(SONFH)是一种因过度使用糖皮质激素导致股骨头塌陷和局部疼痛的疾病。过氧化物酶体增殖物激活受体γ(PPARγ)主要在脂肪组织中表达。Wnt/β-连环蛋白、AMPK等相关信号通路在调节脂肪细胞分化、脂肪酸摄取和储存中起重要作用。骨髓间充质细胞(BMSCs)具有分化为脂肪细胞或成骨细胞的能力,激素的使用上调PPARγ表达,导致BMSCs倾向于成脂分化。脂肪细胞增多影响股骨头的血液供应和代谢,成骨细胞减少导致小梁骨丢失,最终导致股骨头部分或完全缺血性坏死和塌陷。微小RNA(miRNAs)是一类短的非编码RNA,通过抑制靶基因的转录或翻译来调节基因表达,从而影响细胞功能和疾病进展。研究表明,miRNAs通过调节PPARγ脂质代谢相关信号通路影响SONFH的进展。因此,通过靶向干预miRNA差异表达来调节BMSCs中的成脂-成骨细胞分化以改善脂质代谢,可能是一种准确可行的SONFH治疗策略。本文对miRNA介导的PPARγ相关信号通路进行分类总结,阐明其对SONFH脂质代谢的影响,为SONFH的miRNA靶向治疗提供理论参考,进而为SONFH精准医学提供科学依据。

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