Exosomal Manf originated from endothelium regulated osteoclast differentiation by down-regulating NF-κB signaling pathway.

IF 2.8 3区医学 Q1 ORTHOPEDICS Journal of Orthopaedic Surgery and Research Pub Date : 2025-04-07 DOI:10.1186/s13018-025-05671-w

Zhilong Pi, You Wu, Xinyu Wang, Pingyue Li, Renkai Wang

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Abstract

Background: Endothelium-derived exosomes has been reported to enhanced osteogenesis. However, the role of endothelial exosomes on osteoclastgenesis is still unknown.

Methods: 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.

Results: 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.

Conclusion: HUVEC-exosomal Manf suppressed osteoclastogenesis via down-regulating NF-κB signaling.

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外泌体Manf起源于内皮细胞下调NF-κB信号通路调控的破骨细胞分化。

背景：内皮来源的外泌体已被报道能促进成骨。然而，内皮外泌体在破骨细胞发生中的作用尚不清楚。方法：采用人脐静脉内皮细胞（HUVECs）分离外泌体。PBS或HUVEC-Exos处理RAW 264.7细胞。然后，预处理的RAW 264.7细胞进行TRAP染色和RT-qPCR检测。在体内，我们构建了骨质疏松小鼠模型。卵巢切除术后经尾静脉注射PBS或HUVEC-Exos。采用micro-CT和TRAP染色评估骨量。此外，我们进行了RNA测序，发现了差异表达的基因。结果：内皮源性外泌体抑制了破骨细胞的分化。此外，HUVEC-Exos对骨骼具有促进体内骨吸收的特异性作用。此外，外泌体Manf通过下调NF-κB信号通路促进骨吸收，HUVEC-Exos Manf在体内抑制破骨细胞分化。结论：huvec -外泌体Manf通过下调NF-κB信号通路抑制破骨细胞生成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Orthopaedic Surgery and Research ORTHOPEDICS-

CiteScore

4.10

自引率

7.70%

发文量

494

审稿时长

>12 weeks

期刊介绍： Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues. Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications. JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.