Pi Zhilong, Wu You, Wang Xinyu, Li Pingyue, Wang Renkai
Guangzhou University of Chinese Medicine, No. 132, Outer Ring East road, Guangzhou, 510010, Guangdong, China.
Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopaedics, General Hospital of Southern Theater Command of PLA, 111 Liuhua Road, Guangzhou, Guangdong, China.
J Orthop Surg Res. 2025 Apr 7;20(1):349. doi: 10.1186/s13018-025-05671-w.
Endothelium-derived exosomes has been reported to enhanced osteogenesis. However, the role of endothelial exosomes on osteoclastgenesis is still unknown.
Human umbilical vein endothelial cells (HUVECs) were used to isolate exosomes. PBS or HUVEC-Exos were used to treat RAW 264.7 cells. Then, the preconditioned RAW 264.7 cells were subjected to TRAP staining and RT-qPCR assays. In vivo, we constracted osteoporosis mice model. PBS or HUVEC-Exos were injected through tail vein after ovariectomy surgery. Bone mass was assessed by micro-CT and TRAP staining. Furthermore, we conducted RNA sequencing and found the genes that were differentially expressed.
Osteoclast differentiation was inhibited by endothelium-derived exosomes in this study. Moreover, HUVEC-Exos demonstrated a specific action on bones to promote in vivo bone resorption. Furthermore, exosomal Manf promoted bone resorption via down-regulating NF-κB signaling, and HUVEC-Exos Manf inhibited osteoclast differentiation in vivo.
HUVEC-exosomal Manf suppressed osteoclastogenesis via down-regulating NF-κB signaling.
内皮细胞衍生的外泌体已被报道可增强成骨作用。然而，内皮外泌体在破骨细胞生成中的作用仍不清楚。
用人脐静脉内皮细胞（HUVECs）分离外泌体。用PBS或HUVEC-Exos处理RAW 264.7细胞。然后，对预处理的RAW 264.7细胞进行抗酒石酸酸性磷酸酶（TRAP）染色和逆转录定量聚合酶链反应（RT-qPCR）检测。在体内，我们构建了骨质疏松小鼠模型。卵巢切除术后通过尾静脉注射PBS或HUVEC-Exos。通过显微计算机断层扫描（micro-CT）和TRAP染色评估骨量。此外，我们进行了RNA测序并发现了差异表达的基因。
本研究中内皮细胞衍生的外泌体抑制破骨细胞分化。此外，HUVEC-Exos对骨骼具有促进体内骨吸收的特定作用。此外，外泌体中的黑色素瘤衍生生长因子（Manf）通过下调核因子κB（NF-κB）信号促进骨吸收，且HUVEC-Exos Manf在体内抑制破骨细胞分化。
HUVEC外泌体中的Manf通过下调NF-κB信号抑制破骨细胞生成。
