A tale of the good and bad: Cell senescence in bone homeostasis and disease

Historically, cellular senescence has been viewed as an irreversible cell-cycle arrest process with distinctive phenotypic alterations that were implicated primarily in aging and tumor suppression. Recent discoveries suggest that cellular senescence represents a series of diverse, dynamic, and heterogeneous cellular states with the senescence-associated secretory phenotype (SASP). Although senescent cells typically contribute to aging and age-related diseases, accumulating evidence has shown that they also have important physiological functions during embryonic development, late pubertal bone growth cessation, and adulthood tissue remodeling. Here, we review the recent research on cellular senescence and SASP, highlighting the key pathways that mediate senescence cell-cycle arrest and initiate SASP. We also summarize recent literature on the role of cellular senescence in maintaining bone homeostasis and mediating age-associated osteoporosis, discussing both the beneficial and adverse roles of cellular senescence in bone during different physiological stages, including bone development, childhood bone growth, adulthood bone remodeling, and bone aging.