Comprehensive Analysis of lncRNA and miRNA Expression Profiles and ceRNA Network Construction in Osteoporosis
骨质疏松 lncRNA 和 miRNA 表达谱的综合分析及 ceRNA 网络构建
- 作者列表："Zhang, Xianzuo","Liang, Haiyi","Kourkoumelis, Nikolaos","Wu, Zhaodong","Li, Guoyuan","Shang, Xifu
Multiple profiling studies have identified a number of non-coding RNAs associated with the pathogenesis of human diseases. However, the exact regulatory mechanisms and functions of these non-coding RNAs in the development of osteoporosis have not yet been explored. Transcriptome gene expression and miRNA microarray data from peripheral blood monocytes of five high hip bone mineral density (BMD) subjects and five low hip BMD subjects were analyzed. Differentially expressed mRNAs, lncRNAs, and miRNAs were identified and subjected to functional enrichment analysis. Additionally, protein–protein interaction (PPI), lncRNA–mRNA, and mRNA–lncRNA–miRNA competing endogenous RNA (ceRNA) networks were constructed. Differential analysis revealed that 297 mRNAs, 151 lncRNAs, and 38 miRNAs were significantly differentially expressed between peripheral blood monocytes from high and low hip BMD subjects. Key genes including ACLY, HSPA5, and AKT1 were subsequently identified in the PPI network. Additionally, differentially expressed lncRNAs were primarily enriched in the citrate cycle (TCA cycle), biosynthesis of antibiotics, and carbon metabolism pathways. Finally, the mRNA–lncRNA–miRNA network revealed several key ceRNA regulatory relationships among the transcripts and non-coding RNAs. Key mRNAs and non-coding RNAs identified in the networks represent potential biomarkers or targets in the diagnosis and management of osteoporosis. Our findings represent a resource for further functional research on the ceRNA regulation mechanism of non-coding RNA in osteoporosis.
多项分析研究已经确定了许多与人类疾病发病机制相关的非编码 rna。然而，这些非编码 rna 在骨质疏松症发生发展中的确切调控机制和功能尚未被探索。分析了 5 例高髋部骨密度 (BMD) 受试者和 5 例低髋部 BMD 受试者外周血单核细胞的转录组基因表达和 miRNA 微阵列数据。鉴定差异表达的 mRNAs 、 lncRNAs 和 miRNAs，并进行功能富集分析。此外，构建了蛋白质-蛋白质相互作用 (PPI) 、 lncRNA-mRNA 和 mRNA-lncRNA-miRNA 竞争内源性 RNA (ceRNA) 网络。差异分析发现，297 个 mRNAs 、 151 个 lncRNAs 和 38 个 miRNAs 在高、低髋部 BMD 受试者外周血单核细胞之间显著差异表达。包括 ACLY 、 HSPA5 和 AKT1 在内的关键基因随后在 PPI 网络中被鉴定出来。此外，差异表达的 lncRNAs 主要富集在柠檬酸循环 (TCA 循环) 、抗生素生物合成和碳代谢途径中。最后，mRNA-lncRNA-miRNA 网络揭示了转录本和非编码 rna 之间的几个关键 ceRNA 调控关系。网络中确定的关键 mrna 和非编码 rna 代表了骨质疏松症诊断和管理中的潜在生物标志物或靶点。我们的发现代表了对骨质疏松症中非编码 RNA 的 ceRNA 调控机制进行进一步功能研究的资源。
METHODS::Apparent calcium absorption, total bone mineral content and density, and mineral contents of the right femur were studied using a growing rat model. Twenty-four male Wistar rats were fed with diets based on extruded whole grain red (RSD) or white sorghum (WSD), and control diet (CD) up to 60 days. The animals fed with sorghum diets consumed less and gained less weight compared to those fed with CD, but the efficiency of all diets was similar. Calcium intake was lower in animals fed with sorghum diets, related to the lower total intake of these animals. Apparent calcium absorption in animals fed with RSD was lower than in those fed with CD (CD: 72.7%, RSD: 51.0%, WSD: 64.8%). No significant differences in bone mineral density of total body, spin, femur, distal femur, tibia and proximal tibia were observed among the groups. However, Ca and P contents in the right femur of the rats consuming RSD were lower, indicating a certain imbalance in the metabolism of these minerals.
METHODS:OBJECTIVE:Controversy exists about the impact of bone mineral density (BMD) and fracture risk in newly diagnosed patients with breast cancer (BC). It is presumed that there are differences in BMD between women with BC and healthy controls. BMD is therefore considered as a potential marker to predict BC risk. This study was conducted to investigate the association of BMD, trabecular bone score (TBS) and fracture risk in younger postmenopausal women with hormone responsive BC. METHODS:Overall, 343 women were examined. Women with BC were matched to a control group of the general population. Forty-nine women and fifty-nine controls were included in the final analysis. All subjects underwent dual energy x-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and the total hip to evaluate bone mineral density. The 10-year fracture risk for a major osteoporotic fracture was assessed using the FRAX-score and the TBS-adjusted FRAX-Score, respectively. RESULTS:Lumbar and femoral neck BMD were similar in BC patients and controls. No difference was found for TBS of the spine (1.38 ± 0.1 vs.1.36 ± 0.09) in the BC and the control group, respectively (p = 0.19). The 10- year probability for a major osteoporotic fracture (MoF) or femoral neck (FN) fracture was 6.1 (± 2.6%) and 0.9 (± 1.2%) in the BC group vs. 6.7 (± 3.5%) (p = 0.33) and 0.9 (± 1.1%) (p = 0.73) in the control group. CONCLUSION:Postmenopausal women younger than 60 years with breast cancer do not show any differences in baseline BMD, TBS, or TBS adjusted FRAX in comparison to controls.
METHODS::The goals of this study are to evaluate the ability of the multicomponent collagen-elastin-like polypeptide (ELP)-Bioglass scaffolds to support osteogenesis of rat mesenchymal stem cells (rMSCs), demonstrate in vivo biocompatibility by subcutaneous implantation in Sprague-Dawley rats, monitor degradation noninvasively, and finally assess the scaffold's ability in healing critical-sized cranial bone defects. The collagen-ELP-Bioglass scaffold supports the in vitro osteogenic differentiation of rMSCs over a 3 week culture period. The cellular (rMSC-containing) or acellular scaffolds implanted in the subcutaneous pockets of rats do not cause any local or systemic toxic effects or tumors. The real-time monitoring of the fluorescently labeled scaffolds by IVIS reveals that the scaffolds remain at the site of implantation for up to three weeks, during which they degrade gradually. Micro-CT analysis shows that the bilateral cranial critical-sized defects created in rats lead to greater bone regeneration when filled with cellular scaffolds. Bone mineral density and bone microarchitectural parameters are comparable among different scaffold groups, but the histological analysis reveals increased formation of high-quality mature bone in the cellular group, while the acellular group has immature bone and organized connective tissue. These results suggest that the rMSC-seeded collagen-ELP-Bioglass composite scaffolds can aid in better bone healing process.