Zinc Deficiency Induced Mouse Bone Rarefaction And ZnTs

Zinc is an essential trace element which plays critical roles in multiple metabolic and signaling pathways.It is the most abundant trace element in bone.Zinc has been demonstrated to be essential for bone growth,modeling and remodeling.Zinc is thought to exert a direct effect on bone mineralization by its action on nucleation and mineral growth.Skeletal changes,including delayed maturation,reduced bone mass, and osteoporosis have been associated with zinc deficiency.Since the overall body size of vertebrates is primarily determined by longitudinal bone growth at the growth plate, abnormalities in the growth plate may lead to short stature and skeletal deformity.It can be concluded that the specific effects of zinc deficiency on bone are essentially mediated by growth plate dysfunction.However,the molecular mechanism underlies this phenomenon is still unclear.Growth plate is responsible for longitudinal bone growth.Zinc has a positive effect on the growth plate activity and growth.In addition to a decrease in the width of the growth plate,there are specific pathological lesions associated with zinc deficiency. The cells had abnormal shapes and were decreased in number.Changes in cell proliferation,differentiation and apoptosis were manifested in the growth plate. Excluding the possible involvement of indirect effects through the autocrine/paracrine factors,the cell growth of chondrocytes in growth plate can also be disturbed.Thus,it was very likely that this cellular changes in epiphyseal growth plates were directly associated with reduced zinc ions.The intracellular zinc level is strictly regulated by several mechanisms.Recent studies have indicated that the Scl 30 family zinc transporters(ZnTs)may play critical roles in maintaining intracellular zinc homeostasis in mammalian cells.All of the members of this family are thought to facilitate zinc efflux from the cytoplasm either into various intracellular compartments or across the plasma membrane.ZnT family members are predicted to have 6 transmembrane domains with both N- and C-termini on the cytoplasmic side of the membrane and a histidine-rich loop between domainsâ…£andâ…¤,where zinc has been presumed to be bound by histidines and subsequently transported across the membrane.The functions of ZnT family members vary according to tissue type.Some studies,in vitro and in vivo,have proved that ZnT family plays critical roles in bone formation.It has been proved that Znt5-null mice showed significantly poor growth and a high degree of osteopenia.Fluorescent immunostaining analysis has indicated that ZnT5 resides on the membrane of the Golgi apparatus and vesicular compartments and implicated in the entry of zinc into the Golgi lumen.ZnT7 protein also resides in the Golgi apparatus as well as unknown vesicular compartment.Overexpression of this transporter results in accumulation of zinc ions in Golgi apparatus in Chinese hamster ovary(CHO)cells.In this study,we examine the localization of ZnT7 and distribution of chelatable zinc ion pools in the mouse rib growth plate using autometallography techniques.The comparation between the distribution of ZnT7 and zinc ion pools will provide a clue to elucidate the functional roles of ZnT7 in zinc homeostasis in rib chondrocytes.