Short communication: Dietary bovine milk–derived exosomes improve bone health in an osteoporosis-induced mouse model

Abstract

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and fracture susceptibility. In an aged society with increased life expectancy, the incidence rate of osteoporosis is also rapidly increasing. Inadequate nutrition may negatively influence bone metabolism. Recently, many studies have investigated the functionality of milk-derived exosomes, which play important roles in cell-to-cell communication. However, there are few reports of how milk-derived exosomes influence osteoblast proliferation and differentiation. Here, we determined whether bovine colostrum-derived exosomes promote anti-osteoporosis in vitro and in vivo. Tartrate-resistant acid phosphatase-stained cells were significantly inhibited in Raw264.7 cells treated with exosomes, indicating reduced osteoclast differentiation. We induced osteoporosis in mice using glucocorticoid pellets after orally administering exosomes for 2 mo. Interestingly, the bone mineral density of exosome-fed mouse groups was significantly improved compared with the glucocorticoid-induced osteoporosis group without exosome treatment. In addition, Lactobacillus were decreased in the gut microbiota community of osteoporosis-induced mice, but the gut microbiota community composition was effectively restored by exosome intake. Taken together, we propose that exosomes isolated from bovine colostrum could be a potential candidate for osteoporosis prevention, bone remodeling improvement, and inhibition of bone resorption. To our knowledge, this is the first time that a protective effect of milk exosomes against osteoporosis has been demonstrated in vivo. Our results strongly suggest that bovine colostrum exosomes might be used as a prophylaxis to prevent the onset of osteoporosis. Indeed, our results offer promising alternative strategies in the nutritional management of age-related bone complications.

Exosomes derived from cyclic mechanical stretch-exposed bone marrow mesenchymal stem cells inhibit RANKL-induced osteoclastogenesis through the NF-κB signaling pathway

“…Increasing evidence has shown the therapeutic potential of exosomes in treating various bone diseases (30,31). The BMD of bovine colostrum exosome-fed glucocorticoid-induced osteoporosis mice was significantly improved compared with that of control mice without exosome treatment (32). In a femoral fracture model, mice treated with exosomes from human umbilical cord MSCs (HUCMSCs) cultured under hypoxic conditions showed a significantly larger callus volume and greater vascularity in the fracture site than those treated with exosomes from HUCMSCs cultured under normoxic conditions or with PBS (33).…”

Exosomes Derived from Cyclic Mechanical Stretch-exposed Bone Marrow Mesenchymal Stem Cells Inhibit RANKL-induced Osteoclastogenesis through the NF-κB Signaling Pathway

“…Increasing evidence has shown the therapeutic potential of exosomes in treating various bone diseases [30,31]. The bone mineral density of bovine colostrum exosome-fed glucocorticoid-induced osteoporosis mice was signi cantly improved compared with that of control mice without exosome treatment [32]. In a femoral fracture model, mice treated with exosomes from human umbilical cord MSCs (HUCMSCs) cultured under hypoxic conditions showed a signi cantly larger callus volume and greater vascularity in the fracture site than those treated with exosomes from HUCMSCs cultured under normoxic conditions or with PBS [33].…”

Comparative analysis of dietary exosome-derived microRNAs from human, bovine and caprine colostrum and mature milk

“…Taken together, we found that miR-30a-5p, miR-22-3p, and miR-26a are highly conserved in colostrum and mature milk in cows, caprines, and humans, suggesting their possible importance in neonatal growth. Our results provide new insights and resources for discovering the noble functionality of immune-associated miRNAs from dietary exosome [37] and for developing infant formulas taking into account the differences on miRNA expression in human, bovine and caprine milk as well as evaluating biological features as diagnostic biomarkers.…”