Application of Milk Exosomes for Musculoskeletal Health: Talking Points in Recent Outcomes

Abstract

Milk is a nutrient-rich food source, and among the various milks, breast milk is a nutrient source provided by mothers to newborns in many mammals. Exosomes are nano-sized membranous extracellular vesicles that play important roles in cell-to-cell communication. Exosomes originate from endogenous synthesis and dietary sources such as milk. Discovered through electron microscopy as floating vesicles, the existence of exosomes in human milk was confirmed owing to a density between 1.10 and 1.18 g/mL in a sucrose gradient corresponding to the known density of exosomes and detection of MHC classes I and II, CD63, CD81, and CD86 on the vesicles. To date, milk exosomes have been used for treating many diseases, including cancers, and are widely proposed as promising carriers for the delivery of chemotherapeutic agents. However, few studies on milk exosomes focus on geriatric health, especially sarcopenia and osteoporosis related to bone and muscle. Therefore, the present study focused on milk exosomes and their cargoes, which are potential candidates for dietary supplements, and when combined with drugs, they can be effective in treating musculoskeletal diseases. In this review, we introduce the basic concepts, including the definition, various sources, and cargoes of milk exosomes, and exosome isolation and characterization methods. Additionally, we review recent literature on the musculoskeletal system and milk exosomes. Since inflammation and oxidative stress underly musculoskeletal disorders, studies reporting the antioxidant and anti-inflammatory properties of milk exosomes are also summarized. Finally, the therapeutic potential of milk exosomes in targeting muscle and bone health is proposed.

Extracellular Vesicles and Exosomes in the Control of the Musculoskeletal Health

“…Indeed, in C2C12 myocyte cultures, they were reported to increased protein synthesis and myotube size, an effect that was associated with the presence of high levels of miR-149-3p and miR-2881 [ 67 ]. Differently to what reported in the bone, however, at present, such an anabolism-inducing pattern was not confirmed in the whole animal [ 56 ]. Finally, EVs isolated from the plasma of young mice revelaed able to rejuvenate aged satellite cells and to restore the muscle regenerative capacity.…”

“…Recent observations also point to organoid-derived EVs, apparently better than “classical” EVs in terms of amount recovered and effectiveness, as tools potentially useful to treat diseases affecting the bone [ 55 ]. Finally, exosomes derived from bovine milk have been reported to stimulate osteoblast proliferation and differentiation, and to inhibit osteoclast differentiation [ 56 ]. Similar observations were obtained investigating the effect of orally administered colostrum-derived exosomes to mice in which osteoporosis was induced by glucocorticoid treatment or oveariectomy, showing an improvement of bone mineral density associated with restored physiological microbiota [ 57 , 58 ].…”

New insights into dairy management and the prevention and treatment of osteoporosis: The shift from single nutrient to dairy matrix effects—A review

“…Milk and dairy products are a valuable source of minerals, including calcium and phosphorus, high-quality proteins, and essential vitamins. They contain functional ingredients such as oligosaccharides and exosomes that promote bone growth and development and are also good carriers of probiotics (Jia et al, 2023;Kim et al, 2023;Rizzoli & Biver, 2020). It is worth noting that milk is included in the dietary guidelines for the prevention and treatment of osteoporosis in many countries (Huth et al, 2006).…”