Short-Term Zinc Deficiency Inhibits Chondrocyte Proliferation and Induces Cell Apoptosis in the Epiphyseal Growth Plate of Young Chickens

Abstract

The purpose of this study was to investigate the effect of zinc deficiency on chondrocyte proliferation, differentiation and apoptosis in the epiphyseal growth plate of juvenile chickens. Newly hatched broiler chickens were fed either a low zinc (10 mg/kg diet) or a zinc-adequate (68 mg/kg diet) soy protein-based purified diet. Cell proliferation in the growth plate was evaluated with bromodeoxyuridine (BrdU) labeling. Apoptosis was assessed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. Chondrocyte differentiation was evaluated with immunostaining of osteonectin as a marker of maturation. As early as d 3 of feeding, zinc deficiency significantly inhibited chondrocyte proliferation, promoted cell differentiation and induced cell apoptosis in the growth plate. These effects were manifested primarily in areas remote from the blood supply. Immunostaining for local growth factors such as insulin-like growth factor-1 (IGF-1), parathyroid hormone-related protein (PTHrP) and fibroblast growth factor-2 (FGF-2) did not reveal any differences between growth plates of zinc-deficient and zinc-adequate chickens after 3 d of feeding. By d 7, severe growth plate lesions characterized by reduced cellularity and abnormally shaped cells were formed in areas remote from blood vessels. Immunoreactive IGF-1, PTHrP and FGF-2 were all greatly reduced in the lesion. However, the growth rate and food intake of zinc-deficient chickens were not different from those of the controls during the 7-d experiment. Therefore, a direct effect of zinc deficiency on proliferation, differentiation, and apoptosis of growth plate chondrocytes was indicated.

Effect of Zinc Level and Source (Zinc Oxide Vs. Zinc Glycine) on Bone Mechanical and Geometric Parameters, and Histomorphology in Male Ross 308 Broiler Chicken

“…The effect of Zn supplementation on bone development may be due to its direct impact on hormonal growth mediators. The anabolic effect of insulin-like growth factor 1 on osteoblasts is enhanced by Zn (Wang et al, 2002). Moreover, the higher bioavailability of ZnGly indicates that more Zn was absorbed, and not only deposited in bone tissue compared with ZnO, also influenced cell function through its effects on hormones and growth factors.…”

“…It should be noted that the ZnGly50 group presented higher insulinlike growth factor 1 (IGF-1) levels compared with the control group. It is suggested that IGF-1 locally produced in the tissues plays a more important role in growth than that circulating IGF-1 and the produced by the liver (Wang et al, 2002). Cellular changes, which are induced by reduced Zn available from blood supply, are locally observed in areas located away from blood vessels.…”

“…Cellular changes, which are induced by reduced Zn available from blood supply, are locally observed in areas located away from blood vessels. For this reason, it is suggested that longitudinal growth might be very sensitive to Zn status (Wang et al, 2002).…”

Effect of in Utero Cadmium and/or Zinc Exposure on Occurrence of Squeletal Abnormalities.

“…Zn is an essential nutrient for life required for many aspects of fetal growth and plays important roles in both prenatal and postnatal bone development. In fact, studies examining effects of Zn deficiency in animal models have shown that mild to severe Zn deficiency disturbs skeletal growth and maturation (Eberle et al, 1999;Wang et al, 2002). Animals fed on Zn-deficient diets have impairment in growth plate chondrocyte proliferation (Rossi et al, 2001;Wang et al, 2002) and bone mass (Eberle et al, 1999).…”

“…In fact, studies examining effects of Zn deficiency in animal models have shown that mild to severe Zn deficiency disturbs skeletal growth and maturation (Eberle et al, 1999;Wang et al, 2002). Animals fed on Zn-deficient diets have impairment in growth plate chondrocyte proliferation (Rossi et al, 2001;Wang et al, 2002) and bone mass (Eberle et al, 1999). Bone formation in Zn-deficient animals is also characterized by retarded growth plate activity and is associated with reduced cancellous and trabecular volume (Oner et al, 1984;Rossi et al, 2001).…”