Hypoxia, Hypoxia-Inducible Factor-1α (HIF-1α), and Heat-Shock Proteins in Tibial Dyschondroplasia

ABSTRACT Tibial dyschondroplasia (TD) is one of the most prevalent skeletal abnormalities in avian species; it causes economic losses and is an animal welfare problem. It has been hypothesized that the absence of vasculature in the lesion of the TD growth plates at the ends of the long bones is involved in the etiology of the disease. We evaluated the hypoxia status of normal and thiram-induced TD growth plates by immunostaining the protein adducts after pimonidazole hydrochloride administra-tion. In addition, we evaluated the expression of hypoxia-inducible factor-1α (HIF-1α), the major regulator of the hypoxic response that is essential for chondrogenesis, and that of heat-shock proteins (Hsp) downstream from HIF-1α. We demonstrated that, in contrast to the normal growth plates, those afflicted by TD were hypoxic. A major increase in hypoxia was observed in the prolifera-tive, hypertrophic, and calcified zones. In the norma