Department of Gynecology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, People's Republic of China.
Department of Orthopedics, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, People's Republic of China.
Int Immunopharmacol. 2024 Sep 10;138:112611. doi: 10.1016/j.intimp.2024.112611. Epub 2024 Jul 7.
Osteoporosis (OP) is a disease characterized by decreased bone mass, deteriorated microstructure, and increased fragility and fracture risk. The diagnosis and prevention of OP and its complications have become major public health challenges. Therefore, exploring the complex ecological connections between the immune and skeletal systems may provide new insights for clinical prevention and treatment strategies.
First, we performed single-cell RNA sequencing on human lumbar lamina tissue and conducted clustering and subgroup analysis of quality-controlled single-cell transcriptome data to identify target subgroups. Subsequently, enrichment analysis and pseudotime analysis were performed. In addition, we conducted in-depth studies on the gene regulatory network between different cell subgroups and the communication between bone immune cells.
In this study, we identified several cell subgroups that may be involved in the progression of OP. For example, the CCL4 NKT and CXCL8 neutrophils subgroups promote OP progression by mediating an inflammatory environment that disrupts bone homeostasis, and the MNDA Mac subgroup promotes osteoclast differentiation to promote OP. Moreover, the TNFAIP6 Obl, NR4A2 B and HMGN2 erythrocyte subgroups promoted the balance of bone metabolism and suppressed OP. In the cell communication network, Obl closely interacts with immune cell subgroups through the CXCR4-CXCL12, CTGF-ITGB2, and TNFSF14-TNFRSF14 axes.
Our research revealed specific subgroups and intercellular interactions that play crucial roles in the pathogenesis of OP, providing potential new insights for more precise therapeutic interventions for OP.
骨质疏松症（OP）是一种以骨量减少、微观结构恶化、脆性增加和骨折风险增加为特征的疾病。OP 及其并发症的诊断和预防已成为主要的公共卫生挑战。因此，探索免疫系统和骨骼系统之间复杂的生态联系，可能为临床预防和治疗策略提供新的见解。
首先，我们对人腰椎板组织进行了单细胞 RNA 测序，并对经过质量控制的单细胞转录组数据进行聚类和亚群分析，以鉴定目标亚群。随后进行了富集分析和伪时间分析。此外，我们还对不同细胞亚群之间的基因调控网络以及骨免疫细胞之间的通讯进行了深入研究。
在这项研究中，我们确定了几个可能参与 OP 进展的细胞亚群。例如，CCL4 NKT 和 CXCL8 中性粒细胞亚群通过介导破坏骨稳态的炎症环境来促进 OP 的进展，而 MNDA Mac 亚群促进破骨细胞分化以促进 OP。此外，TNFAIP6 Obl、NR4A2 B 和 HMGN2 红细胞亚群促进骨代谢的平衡并抑制 OP。在细胞通讯网络中，Obl 通过 CXCR4-CXCL12、CTGF-ITGB2 和 TNFSF14-TNFRSF14 轴与免疫细胞亚群密切相互作用。
我们的研究揭示了特定的亚群和细胞间相互作用，这些亚群和相互作用在 OP 的发病机制中起着关键作用，为 OP 的更精确治疗干预提供了潜在的新见解。
