Establishing Osteogenic Signaling Networks Through Cell-Type-Specific Proteomic Mapping of Bone Marrow Stem Cell Lineages During Aging

Researcher(s)

  • Aarushi Patel, Biological Sciences, University of Delaware

Faculty Mentor(s)

  • Anja Nohe, Biological Sciences, University of Delaware

Abstract

In previous studies, it was found that age-related changes in bone marrow mesenchymal stem cell (BMSC) differentiation contribute to bone aging. BMSCs primarily differentiate into osteoblasts, while aging shifts differentiation toward adipocytes, reducing bone formation and increasing marrow fat, leading to debilitating diseases like osteoporosis. Proteomic analysis provides insight into the mechanisms underlying this shift at a molecular level. This project compared profiles of young (6-month) and aged (15-month) mice BMSCs to identify osteogenic proteins and signaling pathways associated with aging. Our filtered and sorted proteomic data were compared with publicly available osteogenic datasets from the PRIDE database to generate a curated list of osteogenic protein markers. Proteins were separated by age group, classified as upregulated or downregulated, and analyzed using STRING to identify interaction networks and highly connected hub proteins. Functional enrichment analysis was performed to determine the major biological processes and relevant signaling pathways represented within each network. The 6-month group contained more osteogenic proteins and a greater interconnected network than the 15-month group, showing a stronger activation of pathways involved in bone formation, matrix organization, and endocytosis. However, aged bone exhibited fewer osteogenic proteins and reduced network connectivity, showing impaired osteogenic signaling. These results identify potential proteins and pathways involved in age-related bone formation and provide potential targets for future validation.