ECM1 相关 miR-1260b 通过靶向 GDI1 促进成骨分化。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-01-01 DOI:10.1016/j.acthis.2024.152133
Jiangxia Li , Ke Xu , Yunqing Cui , Tianyuan Xu , Wenchao Fei , Cuiting Lyu , Yinjue Yu , Lina Yang , Yang Hong , Gong Yang
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引用次数: 0

摘要

骨质疏松症(OP)是老年人的常见疾病。促进成骨细胞分化在缓解 OP 症状方面发挥着至关重要的作用。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 基因敲除和 ECM1a 基因过表达的 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,表现为碱性磷酸酶(ALP)活性、基质矿化、Runt相关转录因子2(RUNX2)、骨化蛋白(OPN)、胶原蛋白I(COL1A1)和骨钙蛋白(OCN)蛋白表达的增加,而miR-1260b的低表达则有相反的效果。此外,与非 OP 患者相比,OP 患者的 miR-1260b 表达量减少。接着,我们通过 TargetScan 和 miRDB 预测了 miRNA 的靶基因,发现 miR-1260b 通过直接与 GDP 解离抑制因子 1(GDI1)的 3'- 非翻译区结合,对其进行负调控。随后的实验发现,GDI1 的过表达降低了 ALP 活性和钙沉积,降低了 RUNX2、OPN、COL1A1 和 OCN 的表达水平,并逆转了 miR-1260b 对成骨分化的影响。总之,与 ECM1 相关的 miR-1260b 通过靶向 GDI1 促进了 U2OS 和 MG63 细胞的成骨分化。因此,这项研究对骨质疏松症的治疗具有重要意义。
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ECM1-associated miR-1260b promotes osteogenic differentiation by targeting GDI1

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.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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