Liao Peng, Tong Sihan, Du Lin, Mei Jiong, Wang Bingqi, Lu Yafei, Yao Meng, Zhang Changqing, Liu Delin, Zhong Zhigang, Ye Fang, Gao Junjie
Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
J Orthop Translat. 2025 Jan 8;50:85-96. doi: 10.1016/j.jot.2024.09.013. eCollection 2025 Jan.
Bone marrow inflammaging is a low-grade chronic inflammation that induces bone marrow aging. Multiple age-related and inflammatory diseases involve bone marrow inflammaging. Whether common pathological pathways exist in bone marrow inflammaging remains unclear.
We collected bone marrow from telomerase-deficient mice (telomerase RNA component, TERC), 5 × FAD mice and mice and High-fat diet-fed mice (HFD), and lumbar 5 nerve compression mice. We performed scRNA-Seq analysis on bone marrow obtained from these mouse models to investigate the potential shared pathway of bone marrow inflammation.
We identified the monocyte/macrophage lineage was activated via the App-Cd74 axis in multiple aging and inflammatory mouse models. Increased expression of CD38 and Ly6a, and decreased expression of Col1a and Lif in macrophages serve as shared changes in different mouse models. The activated macrophages, interacting with other cells, control the expansion of B cells via the CD52-Siglec-G axis. The Ccl6-Ccr2 and Ccl9-Ccr1 ligand-receptor pairs, along with Fn1 and C3-related pathways in macrophages, were associated with immune cell activation and the recruitment of lymphocytes. Interactions with mesenchymal cells were enriched for integrins (Itga4), Fn1, and adhesion molecules (Vcam1).
Our study demonstrates that monocyte/macrophage lineage stimulation is a key event in bone marrow inflammaging. We identified common differentially expressed genes and activated pathways in this lineage, suggesting potential targets for future interventions.
Our study revealed shared genes and ligand-receptor pairs in the activated monocyte/macrophage lineage within inflammaging bone marrow. These findings offer potential therapeutic targets for cell-specific anti-inflammatory treatments.
骨髓炎性衰老（inflammaging）是一种导致骨髓衰老的低度慢性炎症。多种与年龄相关的炎症性疾病都涉及骨髓炎性衰老。目前尚不清楚骨髓炎性衰老中是否存在共同的病理途径。
我们收集了端粒酶缺陷小鼠（端粒酶RNA组分，TERC）、5×FAD小鼠、高脂饮食喂养小鼠（HFD）以及腰5神经压迫小鼠的骨髓。我们对从这些小鼠模型获得的骨髓进行了单细胞RNA测序（scRNA-Seq）分析，以研究骨髓炎症的潜在共同途径。
我们发现在多个衰老和炎症小鼠模型中，单核细胞/巨噬细胞谱系通过App-Cd74轴被激活。巨噬细胞中CD38和Ly6a表达增加，Col1a和Lif表达降低是不同小鼠模型中的共同变化。活化的巨噬细胞与其他细胞相互作用，通过CD52-Siglec-G轴控制B细胞的扩增。巨噬细胞中的Ccl6-Ccr2和Ccl9-Ccr1配体-受体对，以及Fn1和C3相关途径与免疫细胞活化和淋巴细胞募集有关。与间充质细胞的相互作用富含整合素（Itga4）、Fn1和黏附分子（Vcam1）。
我们的研究表明，单核细胞/巨噬细胞谱系刺激是骨髓炎性衰老中的关键事件。我们在该谱系中鉴定出了常见的差异表达基因和激活途径，为未来的干预提供了潜在靶点。
我们的研究揭示了炎性衰老骨髓中活化的单核细胞/巨噬细胞谱系中的共享基因和配体-受体对。这些发现为细胞特异性抗炎治疗提供了潜在的治疗靶点。
