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| FNDC5/Irisin调节骨脂平衡治疗糖皮质激素性骨质疏松 |
| FNDC5/irisin regulates bone-fat balance in the treatment of glucocorticoid-induced osteoporosis |
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| DOI：10.3969/j.issn.1006-7108.2026.06.001 |
| 中文关键词: FNDC5 Irisin 糖皮质激素性骨质疏松 骨脂平衡 |
| 英文关键词:FNDC5 Irisin glucocorticoid-induced osteoporosis bone-fat balance |
| 基金项目:广东省自然科学基金项目（2023A1515011071）；云南省临床医学中心重点项目（2024YNLCYXZX0295） |
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| 中文摘要: |
| 目的 探讨FNDC5/Irisin调控骨脂代谢改善糖皮质激素性骨质疏松症（Glucocorticoid-Induced Osteoporosis, GIOP）的效应与机制。方法 体外实验采用鸢尾素（Irisin）干预地塞米松（DEX）诱导的C3H10T1/2间充质干细胞（MSCs）骨脂分化异常细胞模型，通过ALP染色、油红O染色、qPCR检测FNDC5、成骨（ALP、OCN）与成脂（PPARγ、UCP1）基因表达。体内实验通过构建FNDC5过表达及野生型小鼠的GIOP模型，综合体重、骨密度（BMD）、血清生化分析（Irisin、OCN、ALP、TG、TC）、qPCR（股骨FNDC5、ALP、OCN、OPN、OPG、PGC1α与脂肪FNDC5、PPARγ、PGC1α、UCP1、OPN）及病理染色（HE、免疫组化），探讨FNDC5/Irisin调控GIOP小鼠骨脂代谢的在体作用机制。结果 DEX显著抑制MSCs的ALP活性，降低MSCs棕色脂肪分化潜能，下调FNDC5、ALP、OCN、UCP1的表达，并上调PPARγ表达，Irisin干预可有效控制上述异常的发生。野生型GIOP模型小鼠体重上升，BMD下降，股骨微结构破坏，白色脂肪脂滴增大，棕色脂肪形态改变，血清Irisin、OCN、TG、TC水平均一定程度上升高，血清ALP活性被抑制，脂肪UCP1表达被抑制，股骨OPN表达显著上调，FNDC5过表达显著改善上述症状。结论 FNDC5/Irisin通过调控MSCs的分化方向维持骨脂平衡，可能成为GIOP治疗的潜在靶点。 |
| 英文摘要: |
| Objective To investigate the effects and mechanisms of FNDC5/Irisin in regulating bone-fat metabolism to ameliorate glucocorticoid-induced osteoporosis (GIOP). Methods In vitro experiments utilized Irisin intervention in a dexamethasone (DEX)-induced abnormal osteogenic/adipogenic differentiation cell model of C3H10T1/2 mesenchymal stem cells (MSCs). Alkaline phosphatase (ALP) staining, Oil Red O staining, and qPCR were used to detect the expression of FNDC5, osteogenic (ALP, OCN) and adipogenic (PPARγ, UCP1) gene expression. In vivo experiments involved constructing GIOP models in both FNDC5-overexpressing and wild-type mice. Body weight, bone mineral density (BMD), serum biochemical markers (Irisin, OCN, ALP, TG, TC), qPCR (femoral: FNDC5, ALP, OCN, OPN, OPG, PGC1α; adipose: FNDC5, PPARγ, PGC1α, UCP1, OPN), and histopathological staining (H&E, immunohistochemistry) were analyzed to elucidate the regulatory mechanisms of FNDC5/Irisin on bone-fat metabolism in GIOP mice. Results DEX significantly suppressed ALP activity in MSCs, inhibited brown adipocyte differentiation, downregulated FNDC5, ALP, OCN and UCP1 expression, and upregulated PPARγ. Irisin intervention effectively reversed these abnormalities. Wild-type GIOP mice exhibited increased body weight, reduced BMD, disrupted femoral microstructure, enlarged white adipose tissue lipid droplets, altered brown adipose tissue morphology, elevated serum levels of Irisin, OCN, TG, and TC, inhibited serum ALP activity, suppressed adipose UCP1 expression, and significantly upregulated femoral OPN expression. FNDC5 overexpression markedly ameliorated these pathological changes. Conclusion FNDC5/Irisin maintains bone-fat balance by controlling the differentiation direction of MSCs and may become a potential target for GIOP treatment. |
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