Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk
The team of Professor Weidong Tian and Li Liao from West China Hospital of Stomatology, Sichuan University, and the State Key Laboratory of Oral Disease Research has found a novel mechanism based on extracellular vesicles that regulates bone formation in skeletal muscle. The research was published in Cell Metabolism.
As a functional unit of the locomotor system, the skeletal muscle and bone are usually in coordination during development and growth. Skeletal muscle atrophy often leads to bone loss in pathological conditions such as disuse, disease, and aging. Given the global aging trend, sarcopenia has become one of the most common geriatric diseases. Many studies have shown that individuals with sarcopenia have a higher risk of developing osteoporosis. Hence, understanding the molecular communication between skeletal muscle and bone will facilitate the development of more effective strategies for preventing disuse osteoporosis.
In this study, the research team identified that skeletal muscle secreted multiple extracellular vesicles (Mu-EVs). These Mu-EVs traveled through the bloodstream to reach the bone, where they were phagocytized by bone marrow mesenchymal stem/stromal cells (BMSCs). Mu-EVs promoted osteogenic differentiation of BMSCs and protected against disuse osteoporosis in mice. The quantity and bioactivity of Mu-EVs were found to be tightly correlated with the function of skeletal muscle. Proteomic analysis revealed numerous proteins in Mu-EVs, and some of them potentially regulated bone metabolism, especially glycolysis. Subsequent investigations indicated that Mu-EVs promoted glycolysis of BMSCs by delivering lactate dehydrogenase A into these cells.
In conclusion, this study demonstrates that skeletal muscle secretes abundant Mu-EVs. These Mu-EVs promote glycolysis in BMSCs by delivering glycolic profiles to enhance bone formation. Importantly, supplementation of Mu-EVs alleviates disuse osteoporosis following muscle atrophy, suggesting a potential therapeutic strategy.
Shixing Ma and Xiaotao Xing are the co-first authors of this article. Professor Weidong Tian and Li Liao are the corresponding authors. West China Hospital of Stomatology, Sichuan University is the first and major accomplishment unit for this article.
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