Decreased proliferation precedes growth factor changes after physeal irradiation.

The effects of irradiation on growth plate chondrocytes and mediators of chondrocytic differentiation are poorly understood. In earlier work on rat growth plate changes 1/2 to 4 weeks after irradiation, a nadir was identified at 1 week in proliferation and growth factor expression coincident with maximal histomorphometric derangement. The purpose of this study was to determine the earlier sequential relationship of proliferative, growth factor, and histomorphometric changes after irradiation leading to the 1-week nadir. Twenty-four weanling 5-week-old male Sprague-Dawley rats had right knee irradiation with single fraction 17.5 Gy whereas the left leg served as an internal control. The earliest change identified was a significant decrease in BrdU evidence of proliferative activity between 6 and 12 hours after irradiation, which persisted through 48 hours. Twelve to 24 hours after irradiation, caspase-3 staining for apoptosis was higher than that in growth plates not having received radiotherapy. Histomorphometric changes after irradiation were observed as early as 24 hours. Growth factors and their downstream antiapoptotic and proapoptotic mediators did not differ significantly between limbs through 48 hours. The current study suggests that decreased proliferation and apoptosis precede any change in histomorphometric features of the growth plate after irradiation and that decreased growth factor expression occurs later.