Researcher(s)
- Tess Baron, Human Physiology, University of Delaware
Faculty Mentor(s)
- Anja Nohe, Biology, University of Delaware
Abstract
Osteoporosis is a progressive skeletal disease characterized by reduced bone density and structural deterioration, which significantly increases risk of fractures, particularly in women over the age of 65 years old. Bone marrow mesenchymal stem cells (BMSCs) play a critical role in maintaining bone formation and homeostasis, driving bone formation through osteoblast differentiation and paracrine signaling. Although aging impairs the osteogenic potential of BMSCs and direct;y contributes to osteoporosis, the underlying age-related molecular mechanisms are poorly understood.
To address this, this study investigates phosphoproteomic changes in BMSCs in 6-month-old and 15- month-old mice to uncover signaling pathways that are associated with age-related changes decline in osteogenesis. Harvested BMSCs were cultured under unstimulated conditions (US) to try to identify the cause of bone loss. Phosphoprotemic data on BMSCs was analyzed for differentially phosphorylated proteins, enriched biological pathways, and protein interaction networks that are associated with osteogenesis. STRING analysis demonstrated age-dependent differences in protein interaction networks among unstimulated BMSCs from the two age groups. While pathway enrichment analysis highlighted significant enrichment of vesicle-mediated transport, the NuRD complex, and RNA splicing. By comparing the younger and older BMSCs, this research is focused on identifying the age-dependent signaling changes that could influence the osteoblast differentiation and bone formation.
Ultimately, mapping these age-dependent phosphorylation during osteogenic differentiation gives insight to the regulatory pathways that govern bone remodeling throughout aging. These changes may uncover promising molecular targets for therapeutic interventions and preventive strategies against osteoporosis by promoting tissue regeneration and helping to preserve skeletal health.