Figure 3.

Hypothetical working model for cigarette smoke–induced niche changes in human BM. Inhaled tobacco smoke reaches the airways, and nicotine and many other compounds are absorbed into the bloodstream including Cd, Pb, Bz, and acetaldehyde. Smoking induces leukocytosis suggesting HSC activation. Furthermore, smoking increases systemic inflammation and ROS concentrations. Cigarette smoke damages the endothelial cells, possibly by ROS-induced DNA damage or Cd and/or Bz-toxicity and reduces the levels of SCF. Similarly, the survival of MSCs is impaired, possibly due to DNA damage induced by Cd, Pb, or Bz, and they show increased Jagged-1 expression. Acetaldehyde is directly hematotoxic and induces DNA damage in HSCs. Pb suppress proliferation and differentiation of HSCs. However, this is contradictory to the increased leukocytosis observed in smokers. Long-term exposure of Pb reduces trabecular bone volume. Cd suppresses osteogenic and induces adipogenic differentiation of MSCs leading to an expansion of BMAT. BM = bone marrow; BMAT = bone marrow adipose tissue; Bz = benzene; Cd = cadmium; ECs = endothelial cells; HSC = hematopoietic stem cell; MSC = mesenchymal stromal cell; OBs = osteoblasts; OCs = osteoclasts; Pb = lead; ROS = reactive oxygen species; SCF = stem cell factor. Created with BioRender.