Role of the hippo-yap/taz signaling pathway on early response of growth plate to ionizing radiation

Radiotherapy has a major role in the childhood malignancies. The radiation exposure of the growth plates, a highly radiosensitive tissue, is inevitable in despite of advanced radiotherapy techniques. There is a compensatory recovery response in growth plate after the ionizing radiation damage. Unfortunately, this repair response is incomplete and the regulatory mechanisms of radiorecovery doesn't well defined. Our study aims to discover the role of the YAP/TAZ transcriptional co-activators, a major regulator of tissue regeneration, in the response of the growth plate to radiotherapy. In line with this purpose, the distal femur and proximal tibial growth plates of left extremity of 36 weanling rabbits were irradiated with 17.5 Gy radiotherapy in 5 fractions. The rabbits were followed by 1, 7, 10, 14, 17 and 21 days, respectively, in different six groups. The hematoxylin-eosin staining for histomorphological assessment and the immunohistochemical staining for PTHrP, YAP and TAZ was performed. The obtained results were evaluated in comparison with the results of right-sided unirradiated control growth plates. The nuclear expressions of YAP/TAZ decreased during early radiation damage and reached a nadir at one week. The expressions of YAP/TAZ showed apparent increase synchronously with development of radiorecovery. The expressions of PTHrP, YAP and TAZ were lower than controls at each time point. The expression change of YAP/TAZ had correlation to histomorphological and PTHrP changes. These findings showed that YAP/TAZ can play a critical regulatory role both radiation damage and early radiorecovery. Inadequate YAP/TAZ response may be the cause of incompleteness of radiorecovery process.