OMICS Profiling Identifies Signatures of Senescence in Osteogenesis Imperfecta Osteoblasts Counteracted by 4‐PBA

. MS/MS proteomic analysis of conditioned media revealed senescence-associated secretory phenotype proteins, together with components linked to altered cytoskeletal organization and cell adhesion. Transcriptomic analysis identified P53 as a central hub gene, supporting premature senescence activation. Increased senescence-associated β-galactosidase activity, elevated expression of the cyclin-dependent kinase inhibitor P16, and reduced Ki67 levels further supported a senescent phenotype. Notably, senescence-associated proteins were absent from the secretome following 4-PBA treatment, which also modulated cytoskeletal and adhesion-related protein expression. Moreover, 4-PBA significantly reduced senescence marker expression and decreased the number of senescent cells. Overall, these findings indicate that cellular senescence underlies osteoblast dysfunction in OI and uncover a novel contribution of 4-PBA to osteoblast homeostasis.