Shi Wei, Li Dong, Xu Qian, Zhang Kai, Liang Xinyu, Li Hui, Li Zhijun, Zhang Huafeng
Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.
School of integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
BMC Musculoskelet Disord. 2025 Feb 6;26(1):122. doi: 10.1186/s12891-024-08267-3.
Recent studies highlight the role of H-type vasculature in bone regeneration. This study, based on single-cell RNA sequencing (scRNA-seq), aims to explore the changes in H-type vasculature endothelial cells (H_ECs) in osteonecrosis of the femoral head (ONFH) and hip osteoarthritis (HOA), focusing on the death modes such as ferroptosis, pyroptosis, and parthanatos.
We re-analyzed the scRNA-seq data of femoral head samples publicly available in 2022. This study selected nine femoral head samples (3 each from HOA, ONFH stage 3 A, and ONFH stage 4). CD31 + EMCN + endothelial cells were classified as H_ECs. Molecular differences were assessed using Gene Ontology and KEGG analysis. Hypoxia, ferroptosis, pyroptosis, and parthanatos indices were calculated, and transcription factors were predicted using SENIC. Cell communication was analyzed with CellChat.
After integrating the 9 samples, 14 cell types were identified: B cells, Mesenchymal stem cells, Osteoblasts, Endothelial cells, Monocytes, T cells, NK cells, Fibroblasts, Macrophages, Common myeloid progenitors, Chondrocytes, Myelocytes, Osteoclasts, and Pericytes. The number of endothelial cells and H_ECs decreased with necrosis severity. H_ECs showed higher angiogenic capacity but lower stress resistance compared to other endothelial cells. Angiogenic capacity decreased in necrotic samples, accompanied by an elevation in inflammation levels. The hypoxia index was higher, with ferroptosis increased in stage 3 A and parthanatos in stages 3 A and 4. No change was observed in pyroptosis. Cell communication analysis revealed downregulation of SLIT3-ROBO4 signaling during necrosis.
H_ECs show molecular differences compared to other endothelial cells. Ferroptosis and parthanatos contribute to the demise of H_ECs in ONFH, with pericytes and fibroblasts supporting H_EC angiogenesis.
近期研究突显了H型脉管系统在骨再生中的作用。本研究基于单细胞RNA测序（scRNA-seq），旨在探究股骨头坏死（ONFH）和髋骨关节炎（HOA）中H型脉管系统内皮细胞（H_ECs）的变化，重点关注铁死亡、焦亡和PARP-1依赖性坏死等死亡模式。
我们重新分析了2022年公开可得的股骨头样本的scRNA-seq数据。本研究选取了9个股骨头样本（HOA、ONFH 3A期和ONFH 4期各3个）。将CD31+EMCN+内皮细胞分类为H_ECs。使用基因本体论和KEGG分析评估分子差异。计算缺氧、铁死亡、焦亡和PARP-1依赖性坏死指数，并使用SENIC预测转录因子。用CellChat分析细胞通讯。
整合9个样本后，鉴定出14种细胞类型：B细胞、间充质干细胞、成骨细胞、内皮细胞、单核细胞、T细胞、NK细胞、成纤维细胞、巨噬细胞、常见髓系祖细胞、软骨细胞、髓细胞、破骨细胞和周细胞。内皮细胞和H_ECs的数量随坏死严重程度而减少。与其他内皮细胞相比，H_ECs显示出更高的血管生成能力但更低的抗应激能力。坏死样本中的血管生成能力降低，同时炎症水平升高。缺氧指数较高，3A期铁死亡增加，3A期和4期PARP-1依赖性坏死增加。焦亡未观察到变化。细胞通讯分析显示坏死期间SLIT3-ROBO4信号下调。
与其他内皮细胞相比，H_ECs表现出分子差异。铁死亡和PARP-1依赖性坏死导致ONFH中H_ECs的死亡，周细胞和成纤维细胞支持H_EC血管生成。
