Effects of zinc on cell proliferation and proteoglycan characteristics of epiphyseal chondrocytes.

Abstract

Zinc has been postulated as an important nutritional factor involved in growth promotion; however, the cellular mechanisms involved in the effects of zinc on linear growth remain to be elucidated. This study was conducted to evaluate the effects of zinc on the proliferation rate of epiphyseal growth plate chondrocytes and on the structural characteristics of the proteoglycans synthesized by these cells. For these purposes, hypertrophic and proliferating chondrocytes were isolated from the tibiae of 1- and 5-week-old chickens, respectively. Chondrocytes were cultured under serum-free conditions and primary cultures were used. The results showed that zinc stimulated proliferation by 40-50% above the baseline in the case of proliferating chondrocytes, but it had no effect on hypertrophic chondrocytes. Zinc had neither any effects on mean charge density of proteoglycans synthesized by hypertrophic chondrocytes nor in their hydrodynamic size. In contrast, zinc induced an increase in mean charge density and a decrease of hydrodynamic size of proteoglycans synthesized by proliferating chondrocytes. In both cell types zinc had no effect on the composition and hydrodynamic size of the glycosaminoglycan chains. The increased ability of proliferating chondrocytes cultured in the presence of zinc to synthesize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) could be explained by the induction of enzymes participating in the sulfation pathway of proteoglycans. Therefore, the increase in mean charge density of proteoglycans observed in this study may be explained by an increase of the degree of sulfation of proteoglycan molecules. We speculate that the effect of zinc on linear growth may be explained at a cellular level by: a) an increase in proliferation rates of proliferating chondrocytes, and b) increased synthesis of highly charged proteoglycan molecules which decreases mineralization.