IL-6 regulates the bone metabolism and inflammatory microenvironment in aging mice by inhibiting Setd7.

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.