title: Temporal changes in PTHrP, Bcl-2, Bax, caspase, TGF-beta, and FGF-2 expression following growth plate irradiation with or without radioprotectant.
abstract: This study examined temporal changes in growth plate apoptosis molecules and growth factors in an animal model of radiation injury with and without a radioprotectant. Thirty weanling 5-week Sprague-Dawley rats underwent right knee irradiation with single-fraction 17.5 Gy while the left served as internal control. Six animals each were sacrificed at 0.5, 1, 2, 3, or 4 weeks after irradiation. Half of the animals received pretreatment with amifostine (WR-2721) radioprotectant. Immunohistochemical staining for PTHrP, Bcl-2, Bax, caspase-3, FGF-2, and TGF-beta was performed. PTHrP decreased to a nadir at 1 week after irradiation but rebounded to above control levels at 2 weeks in the reserve and transitional zones. The radioprotectant amifostine blunted the decrease in PTHrP but kept PTHrP expression lower than controls during the rebound phase in untreated irradiated animals. Hypertrophic zone Bax expression was decreased by amifostine in both irradiated and non-irradiated limbs at 1 and 2 weeks. FGF, TGF-beta, Bcl-2, and caspase levels generally decreased at 1 week and returned thereafter toward control levels. These findings underscore the importance of PTHrP in response to growth plate irradiation and show the novel finding of a decrease in Bax expression with amifostine pretreatment.
authors.affiliation: Departments of Orthopedics and Pathology, SUNY Upstate Medical University, Syracuse, New York, USA. damront@upstate.edu
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Damron
authors.forename: Sharad
authors.initials: S
authors.lastname: Mathur
authors.forename: Jason A
authors.initials: JA
authors.lastname: Horton
authors.forename: Judith
authors.initials: J
authors.lastname: Strauss
authors.forename: Bryan
authors.initials: B
authors.lastname: Margulies
authors.forename: William
authors.initials: W
authors.lastname: Grant
authors.forename: Cornelia E
authors.initials: CE
authors.lastname: Farnum
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Spadaro
mesh_terms: D004999:Amifostine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D007150:Immunohistochemistry; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D044162:Parathyroid Hormone-Related Protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011837:Radiation-Protective Agents; D016212:Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D016222:Fibroblast Growth Factor 2; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D004999:Amifostine