Studying effects of milk components on bone may have a clinical impact as milk is highly associated with bone maintenance, and clinical studies provided controversial associations with dairy consumption. We aimed to evaluate the impact of milk extracellular vesicles (mEVs) on the dynamics of bone loss in mice. MEVs are nanoparticles containing proteins, mRNA and microRNA, and were supplemented into the drinking water of mice, either receiving diet-induced obesity or ovariectomy (OVX). Mice receiving mEVs were protected from the bone loss caused by diet-induced obesity. In a more severe model of bone loss, OVX, higher osteoclast numbers in the femur were found, which were lowered by mEV treatment. Additionally, the osteoclastogenic potential of bone marrow-derived precursor cells was lowered in mEV-treated mice. The reduced stiffness in the femur of OVX mice was consequently reversed by mEV treatment, accompanied by improvement in the bone microarchitecture. In general, the RANKL/OPG ratio increased systemically and locally in both models and was rescued by mEV treatment. The number of osteocytes, as primary regulators of the RANKL/OPG system, raised in the femur of the OVX mEVs-treated group compared to OVX non-treated mice. Also, the osteocyte cell line treated with mEVs demonstrated a lowered RANKL/OPG ratio. Thus, mEVs showed systemic and local osteoprotective properties in two mouse models of bone loss reflected in reduced osteoclast presence. Data reveal mEV potential in bone modulation, acting via osteocyte enhancement and RANKL/OPG regulation. We suggest that mEVs could be a therapeutic candidate for the treatment of bone loss.

中文翻译：

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牛乳细胞外囊泡通过增加骨细胞数量和靶向 RANKL/OPG 系统在骨质流失实验模型中起到骨保护作用

研究牛奶成分对骨骼的影响可能会产生临床影响，因为牛奶与骨骼维护高度相关，临床研究提供了与乳制品消费的有争议的关联。我们旨在评估牛奶细胞外囊泡 (mEV) 对小鼠骨质流失动力学的影响。MEVs 是包含蛋白质、mRNA 和 microRNA 的纳米颗粒，并被补充到小鼠的饮用水中，无论是接受饮食诱导的肥胖还是卵巢切除术 (OVX)。接受 mEV 的小鼠免受饮食引起的肥胖引起的骨质流失。在更严重的骨质流失模型 OVX 中，发现股骨中的破骨细胞数量更高，而 mEV 治疗降低了这一数量。此外，骨髓源性前体细胞的破骨细胞生成潜力在 mEV 治疗的小鼠中降低。因此，mEV 治疗可以逆转 OVX 小鼠股骨硬度降低，同时改善骨微结构。一般来说，RANKL/OPG 比率在两种模型中全身和局部增加，并且通过 mEV 治疗得以挽救。与 OVX 未治疗小鼠相比，作为 RANKL/OPG 系统主要调节剂的骨细胞数量在 OVX mEVs 治疗组的股骨中增加。此外，用 mEV 处理的骨细胞系表现出降低的 RANKL/OPG 比率。因此，mEV 在两种骨丢失小鼠模型中显示出全身和局部骨保护特性，这反映在破骨细胞的存在上。数据揭示了 mEV 在骨调节中的潜力，通过骨细胞增强和 RANKL/OPG 调节起作用。我们建议 mEV 可能是治疗骨质流失的候选药物。