Inflammation produced by senescent osteocytes mediates age-related bone loss
Zixuan Wang1, Xiaofei Zhang2, Xing Cheng3
1Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Purpose:
The 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.
Methods:
We 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.
Results:
The 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.
Conclusion:
With 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.
Related Concept Videos
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:19The Effect of Aging on Tissues
01:31Osteoclasts in Bone Remodeling
01:40Bone Remodeling
01:30Bone Cells and Tissue
Osteoblasts and Osteocytes
The osteoblast is the bone cell responsible for forming new bone tissue. It is found in the growing portions of bone, including the...
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...