Xu Jinhuang, Tian Zhong, Huang Lina, Yu Yongsheng
J Endocrinol. 2025 Mar 13;265(2). doi: 10.1530/JOE-25-0008. Print 2025 May 1.
Fragility fractures are frequently observed among the elderly population with osteoporosis, and the fundamental process of fracture recovery relies on the differentiation of osteoblasts. LINC01094 was a crucial lncRNA in the regulation of the progression of diseases, but its role in osteoporotic fracture remained unclear. This study was to investigate alterations in the expression of LINC01094 in patients with osteoporotic fractures, evaluate its potential role as a diagnostic biomarker, and explore its effects on osteoblast differentiation. Circulating LINC01094 was tested using serum from 60 healthy individuals, 60 patients with osteoporosis, and 74 patients with osteoporotic fractures by RT-qPCR. The receiver operating characteristic curve was conducted to evaluate its diagnostic performance. The function of LINC01094 was measured in both MC3T3-E1 and BMSC cells. ALP activity detection and ELISA assay were performed to measure the osteogenesis markers, including OCN and Runx2 expression. A dual-luciferase reporter assay was utilized to validate the downstream miR-362-3p of LINC01094 in cells. The expression of circulating LINC01094 was increased in osteoporotic patients with/without fractures than in healthy controls. LINC01094 can differentiate osteoporotic patients from healthy ones and distinguish osteoporotic fracture patients from those without fractures. LINC01094 levels were decreased in osteogenically induced MC3T3-E1 and BMSC cells. miR-362-3p was a direct target of LINC01094, and miR-362-3p partially reversed the effect of LINC01094 in cell viability and differentiation processes. Silencing LINC01094 is crucial for facilitating bone formation and has the potential to serve as both a diagnostic indicator and a treatment target for osteoporosis.
脆性骨折在患有骨质疏松症的老年人群中很常见,而骨折恢复的基本过程依赖于成骨细胞的分化。LINC01094是疾病进展调控中的一种关键长链非编码RNA(lncRNA),但其在骨质疏松性骨折中的作用仍不清楚。本研究旨在调查骨质疏松性骨折患者中LINC01094的表达变化,评估其作为诊断生物标志物的潜在作用,并探索其对成骨细胞分化的影响。通过RT-qPCR检测了60名健康个体、60名骨质疏松症患者和74名骨质疏松性骨折患者血清中的循环LINC01094。绘制受试者工作特征曲线以评估其诊断性能。在MC3T3-E1细胞和骨髓间充质干细胞(BMSC)中检测了LINC01094的功能。进行碱性磷酸酶(ALP)活性检测和酶联免疫吸附测定(ELISA)以测量成骨标志物,包括骨钙素(OCN)和Runx2的表达。利用双荧光素酶报告基因测定法在细胞中验证LINC01094的下游miR-362-3p。与健康对照组相比,有/无骨折的骨质疏松症患者循环LINC01094的表达均升高。LINC01094可以区分骨质疏松症患者与健康人,以及骨质疏松性骨折患者与无骨折患者。在成骨诱导的MC3T3-E1细胞和BMSC细胞中,LINC01094水平降低。miR-362-3p是LINC01094的直接靶点,并且miR-362-3p部分逆转了LINC01094在细胞活力和分化过程中的作用。沉默LINC01094对于促进骨形成至关重要,并且有潜力作为骨质疏松症的诊断指标和治疗靶点。