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Inhibiting uptake of extracellular vesicles derived from senescent bone marrow mesenchymal stem cells by muscle satellite cells attenuates sarcopenia
Journal of Orthopaedic Translation ( IF 6.6 ) Pub Date : 2022-07-06 , DOI: 10.1016/j.jot.2022.06.002
Hanhao Dai 1 , Wu Zheng 2 , Jun Luo 2 , Guoyu Yu 2 , Chao Song 1 , Yijing Wu 1 , Jie Xu 1, 2
Affiliation  

Objective

Osteoporosis is associated with senescence of bone marrow mesenchymal stem cells (BMSCs). Extracellular vesicles derived from senescent BMSCs (BMSC-EVs) could be uptaken by muscle satellite cells (SCs). We hypothesized that inhibiting the uptake of harmful BMSC-EVs by SCs could prevent patients with osteoporosis complicated with sarcopenia.

Methods

Bioinformatics analysis was used to analyze senescent SCs. Myogenic potential of SCs was measured using myogenesis assay and immunofluorescence while muscle atrophy was measured using histological evaluation. And the interaction of cluster of differentiation (CD) 81 and the membrane proteins of SCs was verified using biotin pulldown assay.. CD81-specific siRNA (si-CD81) was used to knockdown CD81 and anti-CD81 antibody (anti-CD81 Ab) was used to block CD81.

Results

Differentially expressed genes in senescent SCs were enriched in muscle cell differentiation. The myogenic potential of senescent SCs was significantly decreased. Senescent BMSC-EVs impaired myogenesis of SCs. CD81 on the surface of BMSC-EVs could bind to membrane proteins of SCs. Both knockdown of CD81 and blocking CD81 prevented the uptake of senescent BMSC-EVs by SCs, thus relieving harmful effects of senescent BMSC-EVs on muscle atrophy.

Conclusion

Blocking CD81 on the surface of senescent BMSC-EVs attenuates sarcopenia in aged mice, which could be useful for prevention of sarcopenia in patients with osteoporosis in clinical practice.

Translational potential of this article

Inhibiting uptake of extracellular vesicles derived from senescent bone marrow mesenchymal stem cells by muscle satellite cells can prevent muscle atrophy in aged mice and has potential for application in treating sarcopenia.



中文翻译:

抑制肌肉卫星细胞对来自衰老骨髓间充质干细胞的细胞外囊泡的摄取可减轻肌肉减少症

客观的

骨质疏松症与骨髓间充质干细胞 (BMSCs) 的衰老有关。来自衰老 BMSCs (BMSC-EVs) 的细胞外囊泡可以被肌肉卫星细胞 (SCs) 摄取。我们假设抑制 SCs 对有害 BMSC-EVs 的摄取可以预防骨质疏松症合并肌肉减少症的患者。

方法

生物信息学分析用于分析衰老的 SCs。使用肌生成测定和免疫荧光测量 SCs 的生肌潜能,而使用组织学评估测量肌肉萎缩。并使用生物素下拉试验验证分化簇(CD)81与SCs膜蛋白的相互作用。CD81特异性siRNA(si-CD81)用于敲低CD81和抗CD81抗体(anti-CD81 Ab)用于阻断 CD81。

结果

衰老 SCs 中差异表达的基因在肌肉细胞分化中富集。衰老 SCs 的生肌潜能显着降低。衰老的 BMSC-EVs 损害了 SCs 的肌生成。BMSC-EVs 表面的 CD81 可以与 SCs 的膜蛋白结合。CD81 的敲低和阻断 CD81 都阻止了 SCs 对衰老 BMSC-EV 的摄取,从而减轻了衰老 BMSC-EV 对肌肉萎缩的有害影响。

结论

在衰老的 BMSC-EVs 表面阻断 CD81 可减轻老年小鼠的肌肉减少症,这可能有助于临床实践中预防骨质疏松症患者的肌肉减少症。

本文的转化潜力

抑制肌肉卫星细胞对来自衰老骨髓间充质干细胞的细胞外囊泡的摄取可以预防老年小鼠的肌肉萎缩,具有治疗肌肉减少症的潜力。

更新日期:2022-07-06
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