The Role of the Hippo-YAP/TAZ Signaling Pathway As a Driver of Early Growth Plate Recovery Response to Irradiation

OBJECTIVEThe growth arrest of epiphyseal plates is an inevitable complication of radiotherapy in most pediatric cancer patients, yet our understanding of the regulatory mechanisms governing the recovery response remains limited. This experiment sought to delve into the roles of yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional co-activators, crucial drivers of the regenerative process, in this recovery response.METHODSIn the study, thirty-six 8-week-old male rabbits underwent radiotherapy targeting the left distal femur and proximal tibia growth plates, while the right extremity served as an unirradiated control. The rabbits were divided into six groups based on post-irradiation time points (1, 7, 10, 14, 17, and 21 days). Histomorphological assessments through hematoxylin-eosin staining and immunohistochemical labeling of PTHrP, YAP1, and TAZ were conducted on the excised growth plates from both irradiated and unirradiated sides.RESULTSThe initial week post-radiotherapy exhibited arresting effects, including increased apoptosis, reduced proliferative activity, and disruption of the columnar structure. Evidence of the recovery response, characterized by regenerative chondrocyte clones, became evident around day 10 and peaked on day 14. Subsequently, cellular and structural degeneration prevailed, with a transition to osteogenesis in the following days. The radiation notably decreased the nuclear immunopositivity ratio of the three molecules. While nuclear expression levels of YAP1 and TAZ initially declined within the 1st week, they subsequently rebounded sharply, though not reaching control levels.CONCLUSIONThese preliminary findings suggest that YAP1 and TAZ could play a pivotal role as regulators in the recovery response of growth plates following irradiation.