Department of Stomatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, 518055 Guangdong, China.
Institute of Stomatological Research, Shenzhen University, Shenzhen, 518055 Guangdong, China.
Dis Markers. 2022 Jun 15;2022:4759172. doi: 10.1155/2022/4759172. eCollection 2022.
The impaired osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) is a major cause of bone remodeling imbalance and osteoporosis. The bicaudal C homologue 1 (BICC1) gene is a genetic regulator of bone mineral density (BMD) and promotes osteoblast differentiation. The purpose of this study is to explore the probable function of BICC1 in osteoporosis and osteogenic differentiation of aged BMSCs.
We examined the GSE116925 microarray dataset obtained from the Gene Expression Omnibus (GEO) database. The GEO2R algorithm identified differentially expressed genes (DEGs) in Sca-1+ BMSCs from young (3 months old) and old (18 months old) mice. Then, to identify the most crucial genes, we used pathway enrichment analysis and a protein-protein interaction (PPI) network. Furthermore, starBase v2.0 was used to generate the regulatory networks between BICC1 and related competing endogenous RNAs (ceRNAs). NetworkAnalyst was used to construct TF-gene networks and TF-miRNA-gene networks of BICC1 and ceRNA. Furthermore, we investigated the expression in aged Sca-1-positive BMSCs.
We detected 923 DEGs and discovered that epidermal growth factor receptor (EGFR) was the top hub gene with a high degree of linkage. According to the findings of the PPI module analysis, EGFR was mostly engaged in cytokine signaling in immune system and inflammation-related signaling pathways. 282 ceRNAs were found to interact with the BICC1 gene. EGFR was not only identified as a hub gene but also as a BICC1-related ceRNA. Then, we predicted 11 common TF-genes and 7 miRNAs between BICC1 and EGFR. Finally, we found that BICC1 mRNA and EGFR mRNA were significantly overexpressed in aged Sca-1-positive BMSCs.
As a genetic gene that affects bone mineral density, BICC1 may be a new target for clinical treatment of senile osteoporosis by influencing osteogenic differentiation of BMSCs through EGFR-related signaling. However, the application of the results requires support from more experimental data.
骨髓间充质干细胞（BMSCs）成骨分化功能受损是导致骨重建失衡和骨质疏松症的主要原因。双尾 C 同源物 1（BICC1）基因是骨密度（BMD）的遗传调控因子，可促进成骨细胞分化。本研究旨在探讨 BICC1 在骨质疏松症和老年 BMSCs 成骨分化中的可能作用。
我们检测了从年轻（3 个月大）和老年（18 个月大）小鼠中分离的 Sca-1+BMSCs 的 GSE116925 微阵列数据集。GEO2R 算法鉴定了年轻和老年 Sca-1+BMSCs 之间的差异表达基因（DEGs）。然后，为了鉴定最关键的基因，我们使用了通路富集分析和蛋白质-蛋白质相互作用（PPI）网络。此外，starBase v2.0 用于生成 BICC1 与相关竞争性内源 RNA（ceRNA）之间的调控网络。NetworkAnalyst 用于构建 BICC1 和 ceRNA 的 TF-基因网络和 TF-miRNA-基因网络。此外，我们还研究了 BICC1 和 EGFR 在老年 Sca-1+阳性 BMSCs 中的表达。
我们检测到 923 个 DEGs，发现表皮生长因子受体（EGFR）是具有高连接度的顶级枢纽基因。根据 PPI 模块分析的结果，EGFR 主要参与细胞因子信号转导和免疫系统炎症相关信号通路。发现 282 个 ceRNA 与 BICC1 基因相互作用。EGFR 不仅被鉴定为枢纽基因，而且是 BICC1 相关的 ceRNA。然后，我们预测了 BICC1 和 EGFR 之间的 11 个共同 TF-基因和 7 个 miRNA。最后，我们发现 BICC1 mRNA 和 EGFR mRNA 在老年 Sca-1+阳性 BMSCs 中显著过表达。
作为影响骨密度的遗传基因，BICC1 可能通过影响 BMSCs 的成骨分化，通过 EGFR 相关信号通路成为治疗老年骨质疏松症的新靶点。然而，该结果的应用需要更多实验数据的支持。
