PurposeThe molecular mechanisms of age-related bone loss are unclear and without valid drugs yet. The aims of this study were to explore the molecular changes that occur in bone tissue during age-related bone loss, to further clarify the changes in function, and to predict potential therapeutic drugs.MethodsWe collected bone tissues from children, middle-aged individuals, and elderly people for protein sequencing and compared the three groups of proteins pairwise, and the differentially expressed proteins (DEPs) in each group were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). K-means cluster analysis was then used to screen out proteins that continuously increased/decreased with age. Canonical signaling pathways that were activated or inhibited in bone tissue along with increasing age were identified by Ingenuity Pathway Analysis (IPA). Prediction of potential drugs was performed using the Connectivity Map (CMap). Finally, DEPs from sequencing were verified by Western blot, and the drug treatment effect was verified by quantitative real-time PCR.ResultsThe GO and KEGG analyses show that the DEPs were associated with inflammation and bone formation with aging, and the IPA analysis shows that pathways such as IL-8 signaling and acute-phase response signaling were activated, while glycolysis I and EIF2 signaling were inhibited. A total of nine potential drugs were predicted, with rapamycin ranking the highest. In cellular experiments, rapamycin reduced the senescence phenotype produced by the H2O2-stimulated osteocyte-like cell MLO-Y4.ConclusionWith age, inflammatory pathways are activated in bone tissue, and signals that promote bone formation are inhibited. This study contributes to the understanding of the molecular changes that occur in bone tissue during age-related bone loss and provides evidence that rapamycin is a drug of potential clinical value for this disease. The therapeutic effects of the drug are to be further studied in animals.

Abstract-Take

As Chinese residents are increasingly concerned about environmental and health issues, the importance of commercial health insurance has come to the fore. Therefore, it is necessary to study the relationship and mechanism between air pollution and commercial health insurance. This paper empirically analyzes the impact and mechanism of air pollution on the sustainable development of Chinese commercial health insurance. The analysis is conducted using the IV-probit and IV-tobit models with thermal inversion as the instrumental variable for air pollution, with Chinese households as the study population and 2018 as the study period. The results show that PM2.5 concentration has a positive and significant effect on both household participation in commercial health insurance and the level of participation, and that residents’ concern is an important channel linking air pollution and commercial health insurance, where pollution reporting plays a negative transmission role, protective behaviors play a positive transmission role, and healthy depreciation plays a positive transmission role. The results of this study contribute to the comprehensive development of China’s social security system and the sustainable development of the commercial health insurance market.