Inhibiting uptake of extracellular vesicles derived from senescent bone marrow mesenchymal stem cells by muscle satellite cells attenuates sarcopenia

Abstract

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.

Keywords

• Sarcopenia
• Osteoporosis
• Senescence
• Extracellular vesicles
• CD81