Aging, which has become a worldwide problem, leads to the degeneration of multiple organs and tissues. Two of the main changes in aging are dysregulation of the tissue microenvironment and abnormal functioning of specific stem cells. Bone marrow stem cells (BMSCs) in the aging microenvironment are not only effector cells but also immunomodulatory cells that change the microenvironment. IL-6 is a primary inflammatory response factor associated with bone diseases. In this study, we stimulated BMSCs with IL-6 to investigate a novel mechanism of age-related osteoporosis. IL-6 activated the TLR2, TLR4 and AKT pathway as well as inhibited the expression of β-catenin and Setd7. In addition, Setd7 expression in the bone tissues of aged mice was suppressed. Setd7 not only promoted BMSC osteogenic differentiation but also mediated proinflammatory gene expression in BMSCs under IL-6 stimulation. Due to its dual functions in BMSCs, Setd7 may be a novel molecular target for age-related osteoporosis prevention and treatment.

衰老已成为世界性问题，导致多个器官和组织退化。衰老的两个主要变化是组织微环境的失调和特定干细胞的异常功能。衰老微环境中的骨髓干细胞（BMSCs）不仅是效应细胞，也是改变微环境的免疫调节细胞。IL-6 是与骨疾病相关的主要炎症反应因子。在这项研究中，我们用 IL-6 刺激 BMSCs 以研究与年龄相关的骨质疏松症的新机制。IL-6 激活 TLR2、TLR4 和 AKT 通路，并抑制 β-catenin 和 Setd7 的表达。此外，老年小鼠骨组织中的 Setd7 表达受到抑制。Setd7 不仅促进 BMSC 成骨分化，而且在 IL-6 刺激下介导 BMSCs 中的促炎基因表达。由于其在 BMSCs 中的双重功能，Setd7 可能成为预防和治疗老年性骨质疏松症的新分子靶点。