Bone formation or regeneration requires the recruitment, proliferation, and osteogenic differentiation of stem/stromal progenitor cells. A potent stimulus driving this process is mechanical loading. Osteocytes are mechanosensitive cells that play fundamental roles in coordinating loading‐induced bone formation via the secretion of paracrine factors. However, the exact mechanisms by which osteocytes relay mechanical signals to these progenitor cells are poorly understood. Therefore, this study aimed to demonstrate the potency of the mechanically stimulated osteocyte secretome in driving human bone marrow stem/stromal cell (hMSC) recruitment and differentiation, and characterize the secretome to identify potential factors regulating stem cell behavior and bone mechanobiology. We demonstrate that osteocytes subjected to fluid shear secrete a distinct collection of factors that significantly enhance hMSC recruitment and osteogenesis and demonstrate the key role of extracellular vesicles (EVs) in driving these effects. This demonstrates the pro‐osteogenic potential of osteocyte‐derived mechanically activated extracellular vesicles, which have great potential as a cell‐free therapy to enhance bone regeneration and repair in diseases such as osteoporosis.

中文翻译：

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人骨髓干/基质细胞成骨是通过机械激活的骨细胞衍生的细胞外囊泡来调节的。

骨形成或再生需要干/基质祖细胞的募集、增殖和成骨分化。驱动这一过程的一个强有力的刺激是机械负荷。骨细胞是机械敏感细胞，通过分泌旁分泌因子在协调负载诱导的骨形成中发挥重要作用。然而，人们对骨细胞向这些祖细胞传递机械信号的确切机制知之甚少。因此，本研究旨在证明机械刺激的骨细胞分泌组在驱动人骨髓干/基质细胞（hMSC）募集和分化方面的效力，并表征分泌组以确定调节干细胞行为和骨力学生物学的潜在因素。我们证明，受到流体剪切作用的骨细胞会分泌一系列独特的因子，这些因子可显着增强 hMSC 的募集和成骨作用，并证明细胞外囊泡 (EV) 在驱动这些效应中的关键作用。这证明了骨细胞衍生的机械激活的细胞外囊泡的促成骨潜力，其作为无细胞疗法具有巨大的潜力，可以增强骨质疏松症等疾病的骨再生和修复。