Intercellular communication via miR-143-containing microvesicles controls osteoblastic bone formation in vivo

Osteoblasts are the only somatic cell type with bone-forming ability. While the cellular and molecular mechanisms underlying their differentiation and function have been identified, their dynamic control in vivo is unclear. By intravital multiphoton microscopy of live bone tissues of osteoblast fluorescent reporter mice, we visualized intact mature osteoblasts in vivo and found that they actively secrete and capture extracellular microvesicles. Microvesicles from mature osteoblasts contain the microRNA miR-143-3p, which inhibits osteoblast differentiation. Osteoblast-specific deletion of miR-143 increased bone formation and miR-143-deficient microvesicles induced recovery from bone defect. In sum, we report a novel mode of intercellular communication in vivo via microRNA-containing extracellular vesicles, which controls bone homeostasis. We performed next-generation sequencing analysis of small RNAs in total mOB-derived large EVs without filtration.

成骨细胞（Osteoblasts）是唯一具备骨形成能力的体细胞类型。尽管其分化与功能的细胞及分子机制已被阐明，但体内的动态调控机制仍未明确。本研究通过对成骨细胞荧光报告基因小鼠的活体骨组织开展活体多光子显微镜（intravital multiphoton microscopy）成像，在体内可视化了完整的成熟成骨细胞，并发现它们可主动分泌并捕获细胞外微囊泡（extracellular microvesicles）。成熟成骨细胞来源的微囊泡含有miR-143-3p，该微小RNA（microRNA）可抑制成骨细胞分化。成骨细胞特异性敲除miR-143可增强骨形成，而缺失miR-143的微囊泡可促进骨缺损修复。综上，本研究报道了一种全新的体内细胞间通讯模式：通过携带微小RNA的细胞外囊泡（extracellular vesicles）调控骨稳态。我们对未经过滤的全部小鼠成骨细胞（mOB）来源的大型细胞外囊泡（large EVs）中的小RNA进行了下一代测序（next-generation sequencing）分析。