The signaling gas hydrogen sulfide (H2S) has recently been implicated in the regulation of bone remodeling and the maintenance of periodontal health. Exploring the underlying mechanisms for this regulation holds promise for the development of new treatment strategies to block bone resorption and stimulate bone regeneration. A recent study by Zhou et al. (Bioactive Materials, 2024) showed that treatment with H2S stimulated changes in the extracellular vesicles (EVs) released by M2 macrophages, enhancing their capacity to promote the osteogenic differentiation of mesenchymal stem cells in vitro. The H2S-stimulated EVs, given together with mesenchymal stem cells (MSCs), also promoted bone regeneration in vivo in a mouse calvarial critical-size defect model. This activity was linked to augmented expression of moesin, a membrane-cytoskeletal linkage protein, which was found at increased levels in EVs from cells stimulated by H2S. The study identifies a new strategy for generating EVs that are pro-osteogenic. It also uncovers a surprising role for moesin in stimulating osteogenesis in MSCs.