Autophagy controls mesenchymal stem cell properties and senescence during bone aging |
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| Authors: | Ying An Liqiang Zhang Rui Yang Daniel H Doro Wenjia Liu Yan Jin |
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| Institution: | 1. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China;2. State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China;3. Xi'an Institute of Tissue Engineering & Regenerative Medicine, Xi'an, Shaanxi, China;4. Department of Stomatology, PLA Army General Hospital, Beijing, China;5. Department of Craniofacial Development and Stem Cell Biology, Dental Institute, Kings College London, London, UK |
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| Abstract: | Bone marrow‐derived mesenchymal stem cells (BMMSCs) exhibit degenerative changes, including imbalanced differentiation and reduced proliferation during aging, that contribute to age‐related bone loss. We demonstrate here that autophagy is significantly reduced in aged BMMSCs compared with young BMMSCs. The autophagy inhibitor 3‐methyladenine (3‐MA) could turn young BMMSCs into a relatively aged state by reducing their osteogenic differentiation and proliferation capacity and enhancing their adipogenic differentiation capacity. Accordingly, the autophagy activator rapamycin could restore the biological properties of aged BMMSCs by increasing osteogenic differentiation and proliferation capacity and decreasing adipogenic differentiation capacity. Possible underlying mechanisms were explored, and the analysis revealed that autophagy could affect reactive oxygen species and p53 levels, thus regulating biological properties of BMMSCs. In an in vivo study, we found that activation of autophagy restored bone loss in aged mice. In conclusion, our results suggest that autophagy plays a pivotal role in the aging of BMMSCs, and activation of autophagy could partially reverse this aging and may represent a potential therapeutic avenue to clinically treat age‐related bone loss. |
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| Keywords: | adipogenesis aging autophagy BMMSCs osteogenesis senile osteoporosis |
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