Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells (USCs), which were noninvasively harvested from unlimited and easily available urine, as a “factory” to obtain extracellular vesicles (USC-EVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition (with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1 (CTHRC1) and osteoprotegerin (OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.

骨质疏松症是一种令人衰弱的骨骼疾病，影响了数百万人。在这里，我们使用了从无限制且易于获取的尿液中无创收集的人类尿液衍生干细胞（USC）作为“工厂”来获得细胞外囊泡（USC-EV），并证明了USC-EVs的全身注射是有效的通过增强成骨细胞的骨形成和抑制破骨细胞的骨吸收来减轻骨质疏松小鼠的骨质流失并保持骨强度。更重要的是，USC-EV的抗骨质疏松特性并未受到USC供体的年龄，性别或健康状况（有或没有骨质疏松症）的明显破坏。机理研究确定，含有1（CTHRC1）和骨保护素（OPG）的胶原蛋白三螺旋重复序列富含USC-EV，是USC-EV诱导的促成骨作用和抗破骨作用所必需的。我们的结果表明，自体USC-EVs通过促进成骨作用和通过转移CTHRC1和OPG抑制破骨细胞作用，代表了一种有望用于骨质疏松的新型治疗剂。