Osteoporosis (OP) is a common disease among older adults. The promotion of osteoblast differentiation plays a crucial role in alleviating OP symptoms. Extracellular matrix protein 1 (ECM1) has been reported to be closely associated with osteogenic differentiation. In this study, we constructed U2OS cell lines with ECM1 knockdown and ECM1a overexpression based on knockdown, and identified the target miRNA (miR-1260b) by sequencing. Overexpression of miR-1260b promoted the osteogenic differentiation of U2OS and MG63 cells, as demonstrated by increased alkaline phosphatase (ALP) activity, matrix mineralization, and Runt-Related Transcription Factor 2 (RUNX2), Osteopontin (OPN), Collagen I (COL1A1), and Osteocalcin (OCN) protein expressions, whereas low expression of miR-1260b had the opposite effect. In addition, miR-1260b expression was decreased in OP patients than in non-OP patients. Next, we predicted the target gene of miRNA through TargetScan and miRDB and found that miR-1260b negatively regulated GDP dissociation inhibitor 1 (GDI1) by directly binding to its 3′-untranslated region. Subsequent experiments revealed that GDI1 overexpression decreased ALP activity and calcium deposit, reduced RUNX2, OPN, COL1A1, and OCN expression levels, and reversed the effects of miR-1260b on osteogenic differentiation. In conclusion, ECM1-related miR-1260b promotes osteogenic differentiation by targeting GDI1 in U2OS and MG63 cells. Thus, this study has significant implication for osteoporosis treatment.

骨质疏松症（OP）是老年人的常见病。促进成骨细胞分化对于缓解OP症状起着至关重要的作用。据报道，细胞外基质蛋白1 (ECM1) 与成骨分化密切相关。在本研究中，我们构建了ECM1敲低和基于敲低的ECM1a过表达的U2OS细胞系，并通过测序鉴定了目标miRNA （miR-1260b）。miR-1260b 的过表达促进了 U2OS 和 MG63 细胞的成骨分化，碱性磷酸酶 (ALP) 活性、基质矿化和 Runt 相关转录因子 2 (RUNX2)、骨桥蛋白 (OPN)、胶原蛋白 I (COL1A1) 增加证明了这一点和骨钙素(OCN) 蛋白表达，而 miR-1260b 的低表达具有相反的效果。此外，OP 患者中的 miR-1260b 表达比非 OP 患者有所降低。接下来，我们通过TargetScan和miRDB预测了miRNA的靶基因，发现miR-1260b通过直接结合GDP解离抑制剂1（GDI1）的3'非翻译区来负向调控GDP解离抑制剂1（GDI1）。随后的实验表明，GDI1过表达降低了ALP活性和钙沉积，降低了RUNX2、OPN、COL1A1和OCN表达水平，并逆转了miR-1260b对成骨分化的影响。总之，ECM1 相关的 miR-1260b 通过靶向 U2OS 和 MG63 细胞中的 GDI1 促进成骨分化。因此，本研究对于骨质疏松症的治疗具有重要意义。