Aging is associated with excessive bone loss that is not counteracted with the development of new bone. However, the mechanisms underlying age-related bone loss are not completely clear. Myeloid-derived suppressor cells (MDSCs) are a population of heterogenous immature myeloid cells with immunosuppressive functions that are known to stimulate tumor-induced bone lysis. In this study, we investigated the association of MDSCs and age-related bone loss in mice. Our results shown that aging increased the accumulation of MDSCs in the bone marrow and spleen, while in the meantime potentiated the osteoclastogenic activity of the CD11b⁺Ly6C^hiLy6G⁺ monocytic subpopulation of MDSCs. In addition, CD11b⁺Ly6C^hiLy6G⁺ MDSCs from old mice exhibited increased expression of c-fms compared to young mice, and were more sensitive to RANKL-induced osteoclast gene expression. On the other hand, old mice showed elevated production of IL-6 and receptor activator of nuclear factor kappa-B ligand (RANKL) in the circulation. Furthermore, IL-6 and RANKL were able to induce the proliferation of CD11b⁺Ly6C^hiLy6G⁺ MDSCs and up-regulate c-fms expression. Moreover, CD11b⁺Ly6C^hiLy6G⁺ MDSCs obtained from old mice showed increased antigen-specific T cell suppressive function, pStat3 expression, and cytokine production in response to inflammatory stimulation, compared to those cells obtained from young mice. Our findings suggest that CD11b⁺Ly6C^hiLy6G⁺ MDSCs are a source of osteoclast precursors that together with the presence of persistent, low-grade inflammation, contribute to age-associated bone loss in mice.

衰老与骨质流失过多有关，而骨质流失过多并不会被新骨的发育所抵消。然而，与年龄相关的骨质流失的机制尚不完全清楚。髓源性抑制细胞 (MDSC) 是一群异质的未成熟髓细胞，具有免疫抑制功能，已知可刺激肿瘤诱导的骨溶解。在这项研究中，我们研究了 MDSC 与小鼠年龄相关性骨质流失的关系。我们的研究结果表明，衰老增加了骨髓和脾脏中 MDSCs 的积累，同时增强了 MDSCs 的 CD11b ⁺ Ly6C ^hi Ly6G ⁺单核细胞亚群的破骨活性。此外，CD11b ⁺ Ly6C^喜Ly6G⁺与年轻小鼠相比，来自老年小鼠的 MDSC 表现出增加的 c-fms 表达，并且对 RANKL 诱导的破骨细胞基因表达更敏感。另一方面，老年小鼠在循环中表现出 IL-6 和核因子 kappa-B 配体 (RANKL) 受体激活剂的产生升高。此外，IL-6 和 RANKL 能够诱导 CD11b ⁺ Ly6C ^hi Ly6G ⁺ MDSCs 的增殖并上调 c-fms 表达。此外，CD11b ⁺ Ly6C ^hi Ly6G ⁺与从年轻小鼠获得的细胞相比，从老年小鼠获得的 MDSC 显示出增加的抗原特异性 T 细胞抑制功能、pStat3 表达和响应炎症刺激的细胞因子产生。我们的研究结果表明，CD11b ⁺ Ly6C ^hi Ly6G ⁺ MDSCs 是破骨细胞前体的来源，与持续性低度炎症的存在一起，导致小鼠与年龄相关的骨质流失。