Department of Sports Medicine, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China; Department of Sports Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China; The School of Pharmacy, Fujian Medical University, Fuzhou, China.
The School of Clinical Medical, Fujian Medical University, Fuzhou, China.
Bone. 2024 Jun;183:117074. doi: 10.1016/j.bone.2024.117074. Epub 2024 Mar 20.
Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent and incapacitating condition that affects the hip joint. Unfortunately, early diagnostic and treatment measures are limited.
Our study employed Tandem Mass Tag (TMT) labeling mass spectrometry (MS)-based quantitative proteome to compare the proteins of femoral head tissues in patients with SONFH with those of patients who sustained femoral neck fracture (FNF). We investigated the level and effects of glucose transporter member 1 (GLUT1) in SONFH patients and MC3T3-E1 cells and examined the function and molecular mechanism of GLUT1 in the context of SONFH using in vivo and in vitro approaches.
The SONFH group exhibited significant changes in protein expression levels compared to the fracture group. Specifically, we observed the up-regulation of 86 proteins and the down-regulation of 138 proteins in the SONFH group. Among the differentially expressed proteins, GLUT1 was down-regulated and associated with glucose metabolic processes in the SONFH group. Further analysis using Parallel Reaction Monitoring (PRM), WB, and PCR confirmed that the protein was significantly down-regulated in both femoral head tissue samples from SONFH patients and dexamethasone-treated MC3T3-E1 cells. Moreover, overexpression of GLUT1 effectively reduced glucocorticoid (GC)-induced apoptosis and the suppression of osteoblast proliferation and osteogenic differentiation in MC3T3-E1 cells, as well as GC-induced femoral head destruction in GC-induced ONFH rat models. Additionally, our research demonstrated that GC down-regulated GLUT1 transcription via glucocorticoid receptors in MC3T3-E1 cells.
GLUT1 was down-regulated in patients with SONFH; furthermore, down-regulated GLUT1 promoted apoptosis and inhibited osteoblast ossification in dexamethasone-induced MC3T3-E1 cells and contributed to GC-induced femoral head destruction in a SONFH rat model. Glucocorticoids inhibited the transcriptional activity of GLUT1, leading to a reduction in the amount and activity of GLUT1 in the cells and ultimately promoting apoptosis and inhibiting osteoblast ossification via the GC/GR/GLUT1 axis in SONFH.
激素诱导性股骨头坏死（SONFH）是一种普遍且使人丧失能力的疾病，影响髋关节。不幸的是，早期的诊断和治疗措施有限。
我们的研究采用串联质量标签（TMT）标记质谱（MS）-基于定量蛋白质组学比较 SONFH 患者和股骨颈骨折（FNF）患者股骨头组织的蛋白质。我们研究了 SONFH 患者和 MC3T3-E1 细胞中葡萄糖转运蛋白 1（GLUT1）的水平和作用，并通过体内和体外方法研究了 GLUT1 在 SONFH 中的功能和分子机制。
SONFH 组与骨折组相比，蛋白质表达水平有显著变化。具体来说，我们观察到 SONFH 组中有 86 种蛋白质上调，138 种蛋白质下调。在差异表达的蛋白质中，GLUT1 下调，与 SONFH 组中葡萄糖代谢过程有关。使用平行反应监测（PRM）、WB 和 PCR 的进一步分析证实，SONFH 患者的股骨头组织样本和地塞米松处理的 MC3T3-E1 细胞中，蛋白质表达显著下调。此外，GLUT1 的过表达有效减少了 MC3T3-E1 细胞中糖皮质激素（GC）诱导的细胞凋亡以及对成骨细胞增殖和成骨分化的抑制，以及 GC 诱导的 SONFH 大鼠模型中的股骨头破坏。此外，我们的研究表明，GC 通过 MC3T3-E1 细胞中的糖皮质激素受体下调 GLUT1 的转录。
GLUT1 在 SONFH 患者中下调；此外，下调的 GLUT1 促进了地塞米松诱导的 MC3T3-E1 细胞中的细胞凋亡和抑制成骨细胞成骨，并通过 GC/GR/GLUT1 轴促进了 SONFH 大鼠模型中的 GC 诱导的股骨头破坏。糖皮质激素抑制 GLUT1 的转录活性，导致细胞中 GLUT1 的数量和活性减少，最终通过 GC/GR/GLUT1 轴促进 SONFH 中的细胞凋亡和抑制成骨细胞成骨。
