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整合转录组学和蛋白质组学数据,从全面的分子角度探讨肌肉减少症和骨质疏松症之间的关联。

Integrating transcriptomic and proteomic data for a comprehensive molecular perspective on the association between sarcopenia and osteoporosis.

机构信息

The Third Affiliated Hospital of Guangxi University of Chinese Medicine, Liuzhou, 545000, PR China; Department of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350000, PR China.

Department of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350000, PR China; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350000, PR China.

出版信息

Arch Gerontol Geriatr. 2024 Oct;125:105486. doi: 10.1016/j.archger.2024.105486. Epub 2024 May 11.

Abstract

BACKGROUND

Osteoporosis and sarcopenia are common age-related conditions characterized by the progressive loss of bone density and muscle mass, respectively. Their co-occurrence, often referred to as osteosarcopenia, presents significant challenges in elderly care due to increased fragility and functional impairment. Existing studies have identified shared pathological mechanisms between these conditions, including inflammation, hormonal imbalances, and metabolic dysregulation, but a comprehensive understanding of their molecular interplay remains incomplete.

OBJECTIVE

This study aims to deepen our understanding of the molecular interactions between sarcopenia and osteoporosis through an integrated omics approach, revealing potential therapeutic targets and biomarkers.

METHODS

Employing a combination of proteomics and transcriptomics analyses, this study analyzed bone and muscle tissue samples from patients diagnosed with osteoporosis and osteosarcopenia. Techniques included high-throughput sequencing and label-free proteomics, supported by advanced bioinformatics tools for data analysis and functional annotation of genes and proteins.

RESULTS

The study found marked differences in gene and protein expressions between osteoporosis and osteosarcopenia tissues. Specifically, genes like PDIA5, TUBB1, and CYFIP2 in bone, along with MYH7 and NCAM1 in muscle, exhibited differential expression at both mRNA and protein levels. Pathway analyses revealed the significance of oxidative-reduction balance, cellular metabolism, and immune response in the progression of these conditions. Importantly, the study pinpointed osteoclast differentiation and NF-kappa B signaling pathways as critical in the molecular dynamics of osteosarcopenia, suggesting potential targets for therapy.

CONCLUSIONS

This study utilized transcriptomics and proteomics to identify key genes and proteins impacting sarcopenia and osteoporosis, employing advanced network tools to delineate interaction networks and crucial signaling pathways. It highlighted genes like PDIA5 and TUBB1, consistently expressed in both analyses, involved in pathways such as osteoclast differentiation and cytokine interactions. These insights enhance understanding of the molecular interplay in bone and muscle degeneration with aging, suggesting directions for future research into therapeutic interventions and prevention strategies for age-related degenerative diseases.

摘要

背景

骨质疏松症和肌肉减少症是常见的与年龄相关的疾病,分别表现为骨密度和肌肉质量的逐渐丧失。由于脆性增加和功能障碍,它们的同时发生,通常被称为骨肌减少症,给老年护理带来了重大挑战。现有研究已经确定了这些疾病之间存在共同的病理机制,包括炎症、激素失衡和代谢失调,但对它们的分子相互作用还没有全面的了解。

目的

本研究旨在通过综合组学方法深入了解肌肉减少症和骨质疏松症之间的分子相互作用,揭示潜在的治疗靶点和生物标志物。

方法

本研究采用蛋白质组学和转录组学分析相结合的方法,分析了骨质疏松症和骨肌减少症患者的骨和肌肉组织样本。使用高通量测序和无标记蛋白质组学等技术,结合先进的生物信息学工具,对基因和蛋白质进行数据分析和功能注释。

结果

研究发现,骨质疏松症和骨肌减少症组织中的基因和蛋白质表达存在明显差异。具体来说,骨组织中的 PDIA5、TUBB1 和 CYFIP2 基因,以及肌肉组织中的 MYH7 和 NCAM1 基因,在 mRNA 和蛋白质水平上都有差异表达。通路分析显示,氧化还原平衡、细胞代谢和免疫反应在这些疾病的进展中具有重要意义。重要的是,该研究指出破骨细胞分化和 NF-kappa B 信号通路在骨肌减少症的分子动力学中至关重要,这为治疗提供了潜在的靶点。

结论

本研究利用转录组学和蛋白质组学技术鉴定了影响肌肉减少症和骨质疏松症的关键基因和蛋白质,运用先进的网络工具描绘了相互作用网络和关键信号通路。研究强调了 PDIA5 和 TUBB1 等基因的作用,这些基因在两种分析中都有表达,涉及破骨细胞分化和细胞因子相互作用等途径。这些见解增强了对衰老过程中骨和肌肉退化的分子相互作用的理解,为进一步研究治疗干预和预防与年龄相关的退行性疾病的策略提供了方向。

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