Figure 2.

Hypothetical working model for ethanol-induced niche changes in human BM. Ingested alcohol is rapidly absorbed through the gastrointestinal tract into the bloodstream. Ethanol is metabolized mainly in the liver to acetaldehyde and acetate, which generates high levels of ROS. Chronic excessive alcohol consumption is associated with pancytopenia and increased circulatory levels of proinflammatory cytokines. However, the inflammatory status of the HSC niche during excessive alcohol consumption remains unknown. The increased ROS levels induce MSC senescence and reduced proliferation. Furthermore, ROS inhibit osteogenic and promote adipogenic differentiation of MSCs. In addition, ethanol diet reduces trabecular bone volume. Acetaldehyde is directly hematotoxic and induces DNA damage in HSCs. Normally, acetaldehyde is rapidly converted to acetate by aldehyde dehydrogenase, but the enzymes may be lost or saturated leading to increased acetaldehyde. BM = bone marrow; ECs = endothelial cells; EtOH = ethanol; HSC = hematopoietic stem cell; MSC = mesenchymal stromal cell; OBs = osteoblasts; OCs = osteoclasts; ROS = reactive oxygen species. Created with BioRender.