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PMID: 8694787 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins.

The Biochemical journal ·Vol. 317 ( Pt 1) ·1996-07-01 ·Pages 59-64

Hunter GK, Hauschka PV, Poole AR, Rosenberg LC, Goldberg HA

Abstract

Many proteins found in mineralized tissues have been proposed to function as regulators of the mineralization process, either as nucleators or inhibitors of hydroxyapatite (HA) formation. We have studied the HA-nucleating and HA-inhibiting properties of proteins from bone [osteocalcin (OC), osteopontin (OPN), osteonectin (ON) and bone sialoprotein (BSP)], dentine [phosphophoryn (DPP)] and calcified cartilage [chondrocalcin (CC)] over a wide range of concentrations. Nucleation of HA was studied with a steady-state agarose gel system at sub-threshold [Ca] x [PO4] product. BSP and DPP exhibited nucleation activity at minimum concentrations of 0.3 microgram/ml (9 nM) and 10 micrograms/ml (67 nM) respectively. OC, OPN, ON and CC all lacked nucleation activity at concentrations up to 100 micrograms/ml. Inhibition of HA formation de novo was studied with calcium phosphate solutions buffered by autotitration. OPN was found to be a potent inhibitor of HA formation [IC50 = 0.32 microgram/ml (0.01 microM)] whereas OC was of lower potency [IC50 = 6.1 micrograms/ml (1.1 microM)]; BSP, ON and CC all lacked inhibitory activity at concentrations up to 10 micrograms/ml. The effect of OPN on HA formation de novo is mainly to inhibit crystal growth, whereas OC delays nucleation. These findings are consistent with the view that BSP and DPP may play roles in the initiation of mineralization in bone and dentine respectively. OPN seems to be the mineralized tissue protein most likely to function in the inhibition of HA formation, possibly by preventing phase separation in tissue fluids of high supersaturation.

MeSH Terms
Animals Calcification, Physiologic/drug effects Calcium-Binding Proteins/pharmacology Cattle Cell-Free System Chickens Durapatite/metabolism Phosphoproteins/pharmacology Sialoglycoproteins/pharmacology Swine
Chemicals
Calcium-Binding Proteins Phosphoproteins Sialoglycoproteins Durapatite
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hunter G K
Faculty of Dentistry, University of Western Ontario, London, Canada.
Hauschka P V
Poole A R
Rosenberg L C
Goldberg H A
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3170059
Published
1996-07-01
Pages
59-64
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1217486
Subset
IM
Grants
NIAMS NIH HHS · AR 38349 · United States
NIAMS NIH HHS · AR 41392 · United States
External Links
PubMed source DOI: 10.1042/bj3170059 PMC Full Text View journal details
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