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miRNA介导的PPARγ相关信号通路对激素性股骨头坏死脂代谢的影响研究进展

高海源¹, 王晓萍², 周明旺^3,*, 杨星¹, 何帮靖¹

¹甘肃中医药大学中医临床学院，兰州 730000；²甘肃省中医院转化医学研究中心，兰州 730050；³甘肃省中医院关节矫形科，兰州 730050

摘要

激素性股骨头坏死(steroid-induced osteonecrosis of femoral head, SONFH)是一种因过度使用糖皮质激素类药物引起的以股骨头塌陷为特征并伴有局部疼痛等症状的疾病。过氧化物酶体增殖物激活受体-γ (peroxisome proliferator-activated receptor-γ, PPARγ)主要在脂肪组织中表达。Wnt/β-catenin、AMPK等相关信号通路在调节脂肪细胞分化、脂肪酸摄取和存储等方面发挥重要作用。骨髓间充质干细胞(bone marrow mesenchymal stem cells, BMSCs)具有分化为成脂细胞或成骨细胞的能力，而激素的使用会使PPARγ高表达，导致BMSCs偏向成脂分化，成脂细胞增多影响股骨头的血供和代谢，成骨细胞减少使骨小梁缺失，最终致股骨头部分或全部缺血坏死、塌陷。微小RNA (microRNA, miRNA)是一类短链非编码RNA，其可以通过抑制靶基因的转录或翻译来调控基因表达，从而影响细胞功能和疾病进程。研究表明miRNA通过调控PPARγ脂代谢相关信号通路影响SONFH的病变进程，因此，通过靶向干预miRNA差异表达来调控BMSCs中成脂-成骨细胞分化进而改善脂代谢或许是一种精准可行的SONFH治疗策略。本文通过将miRNA介导的PPARγ相关信号通路进行分类归纳，阐明其对SONFH脂代谢的作用机制，为miRNA靶向治疗SONFH提供理论参考，进而为SONFH精准医疗提供科学证据。

关键词： 激素性股骨头坏死; 微小RNA (miRNA); PPARγ; 脂代谢; 信号通路

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

GAO Hai-Yuan¹, WANG Xiao-Ping², ZHOU Ming-Wang^3,*, YANG Xing¹, HE Bang-Jing¹

¹School of Clinical Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China；²Translational Medicine Research Center, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China；³Department of Orthopedics and Joint Surgery, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China

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.

Key words: steroid-induced osteonecrosis of femoral head; microRNA (miRNA); PPARγ; lipid metabolism; signaling pathways

收稿日期：　　录用日期：

通讯作者：周明旺　　E-mail:

DOI: 10.13294/j.aps.2025.0044

引用本文：

高海源, 王晓萍, 周明旺, 杨星, 何帮靖. miRNA介导的PPARγ相关信号通路对激素性股骨头坏死脂代谢的影响研究进展[J]. 生理学报 2025; 77 (3): 493-503.

GAO Hai-Yuan, WANG Xiao-Ping, ZHOU Ming-Wang, YANG Xing, HE Bang-Jing. Research progress on the effect of miRNA-mediated PPARγ-related signaling pathways on lipid metabolism in steroid-induced osteonecrosis of femoral head. Acta Physiol Sin 2025; 77 (3): 493-503 (in Chinese with English abstract).