Jinpeng Wang , Sen Li , Qiao Li , Qiuxin Yan , Yunhao Wang , Xiangyin Zeng , Fan Yang , Siyu Jiang , Manrui Zhang , Yaning Pi , Raza Tahir , Lijun Wei
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引用次数: 0
Abstract
Aims
Astronauts experience weightlessness-induced bone loss (WIBL) due to an imbalanced bone remodeling process involving bone mesenchymal stem cells (BMSCs), osteoblasts, and osteoclasts. Senescence is an important factor contributes to WIBL. In the current study, the effects of Alda-1 on senescence and WIBL were evaluated.
Materials and methods
We used the 2D-Rotating Wall Vessel bioreactor and hindlimb suspension rats, the classic cellular and animal models simulating microgravity (SMG). Aging, osteogenic differentiation, osteoclastic differentiation, and lipogenic differentiation were evaluated in the cell and animal models. Differentially expressed proteins in the femurs of rats were further analyzed using bioinformatics analysis. In addition, mitochondrial membrane potential, reactive oxygen species (ROS) production, and mitophagy markers were identified to estimate mitochondrial activity.
Key findings
It was revealed that SMG accelerated senescence including osteoblasts, BMSCs, and inhibited senescence of RAW264.7 cells. SMG suppressed osteogenesis while promoting osteoclastogenesis and adipogenesis during cell senescence and bone loss. Aldehyde dehydrogenase-2 (ALDH2) was negatively related to WIBL. It was mainly enriched in mitochondria and involved in oxidative stress pathways. Finally, it was proved that Alda-1 significantly promoted ALDH2 levels. Alda-1 exhibited a robust protective response against senescence and WIBL by eliminating ROS accumulation, restoring mitophagy, and protecting cells and bone from apoptosis.
Significance
Our study indicate that Alda-1 exerts a protective effect against SMG-induced skeletal aging and bone loss through mitophagy. It provides a theoretical basis for advancing therapeutic options against WIBL in space.
期刊介绍：
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
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