title: Regulatory effect of endogenous zinc and inhibitory action of toxic metal ions on calcium accumulation by matrix vesicles in vitro.
abstract: Matrix vesicles (MV) isolated from chicken growth plate by collagenase digestion and incubated in 45Ca-labelled synthetic cartilage lymph (SCL) rapidly induce mineral formation. 45Ca uptake occurs in three distinct stages: (1) an initial lag period of limited accumulation, (2) a period of rapid ion uptake and (3) an extended period of slower uptake. Treatment of MV with buffered aqueous 1,10-phenanthroline (OP), a metal ion chelator, eliminated the lag period, promoting immediate, enhanced Ca2+ uptake. Analysis of MV for trace metals showed them to contain relatively high concentrations of Zn (1.58 mumol/g MV) and lesser amounts of Cu (0.07 mumol/g MV). At least 30-40% of the Zn was readily extractable in isosmotic buffers. Addition of Zn to SCL at levels as low as 5 microM completely inhibited MV mineralization; addition of OP to Zn-inhibited MV restored their ability to mineralize. The findings suggest that Zn2+ ions act as an endogenous regulator of MV Ca2+ uptake and that the normal lag period results from a competition between Zn2+ and Ca2+ for high affinity Ca2+ binding sites in the MV membrane or within the MV lumen. Other metals tested included Cu2+, Pb2+ and Cd2+ which had little or no effect on MV mineralization, Mn2+, which had an intermediate effect, and Al3+, which was found to be almost as inhibitory as Zn2+. This finding may have implications for aluminum-associated osteomalacia.
authors.affiliation: Department of Chemistry, University of South Carolina, Columbia 29208.
authors.forename: G R
authors.initials: GR
authors.lastname: Sauer
authors.forename: H D
authors.initials: HD
authors.lastname: Adkisson
authors.forename: B R
authors.initials: BR
authors.lastname: Genge
authors.forename: R E
authors.initials: RE
authors.lastname: Wuthier
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002645:Chickens; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008670:Metals / Q000633:toxicity*; D015032:Zinc / Q000502:physiology*
chemical_list: D008670:Metals; D015032:Zinc; D002118:Calcium