Fig. 8

Milk exosome and bone homeostasis. MiRs play a key role in the regulation of bone remodeling executed by bone-resorbing osteoclasts and bone-forming osteoblasts. Blood monocytes are a primary source of osteoclast precursor cells. Upregulation of receptor activator of nuclear factor B ligand (RANKL), V-Fos FBJ murine osteosarcoma viral oncogene homolog (c-Fos) and transforming growth factor-β (TGF-β) promote osteoclastogenesis. miR-148a via targeting V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) increases RANKL expression. miR-21 via targeting programmed cell death 4 (PDCD4) increases c-Fos activity. Notably, miR-148a, miR-21 and TGF-β are provided by dairy milk exosomes. Addition of commercial milk-derived exosomes to bone marrow-derived osteoclast precursor cells increased osteoclast formation. Overexpression of miR-148a triggers mesenchymal stem cells (MCS) to differentiate into adipocytes and attenuates osteoblast differentiation. Persistent intake of dairy milk exosomes may thus disturb the delicate balance of bone remodeling favoring osteoclastogenesis over osteoblastogenesis, a critical mechanism promoting osteoporosis and fracture risk