Altered Senescence-Associated Secretory Phenotype of Human Osteoblasts from Patients with Osteoporosis Enhances...

Osteoporosis (OP) is a highly prevalent age-associated inflammatory bone disease that remains underdiagnosed and undertreated despite its substantial global burden. OP is characterized by impaired osteoblast (OB) function, alterations in the extracellular matrix and chronic, low-grade inflammation associated with aging ('inflammaging'). Initial evidence suggests that the accumulation of senescent cells and their senescence-associated secretory phenotype (SASP) may contribute to disease progression. Additionally, growing evidence indicates a close relationship between osteogenesis and angiogenesis in OP. This study aimed to characterize senescence-associated secretory changes in primary human OBs from donors with OP and to assess their functional impact on endothelial cell behavior. Primary human OBs from donors with OP (n = 15; female: 9, male: 6) and without OP (n = 21; female: 14, male: 7) were analyzed for senescence-associated secretory profiles using ELISA, proteome arrays, and Western blot analysis. The effects of OB-conditioned media on endothelial cell behavior were assessed in endothelial cell migration assays. OBs from donors with OP showed a tendency toward increased senescence-associated features in the β-galactosidase assay, alongside an altered secretory phenotype characterized by increased IL-6, reduced IL-8 and angiogenin levels and decreased expression of extracellular matrix-associated proteins, such as osteopontin, osteonectin, progranulin and thrombospondin-1. Conditioned media from OBs from donors with OP significantly enhanced endothelial cell migration and proliferation in vitro. These findings suggest that OBs from donors with OP exhibit a SASP that may alter the angiogenic microenvironment in the bone.