Abstract

A brief review of the various theories of bone mineralization is presented. It is not clear at present whether the many mineralization events which have been proposed are redundant or cooperative. A short description is given of homogeneous and heterogeneous nucleation of solids from solution and how these mechanisms affect hydroxyapatite formation, in vitro and in vivo. The remainder of the paper deals with specific experiments by the authors on (a) the stabilization of amorphous calcium phosphate and (b) the inhibitory role of proteoglycans in preventing cartilage mineralization. Stable amorphous calcium phosphate is found in the mitochondria of cells involved in tissue mineralization. In addition, it is believed that in bone mineral deposition an unstable amorphous calcium phosphate is formed first before transforming to bone apatite. A number of chemical species have been shown to act as stabilizers of amorphous calcium phosphate. The example given here in detail is the stabilization of the amorphous granules found in mitochondria by a mixture of Mg and adenosine triphosphate. The effect of proteoglycan aggregates and subunits from calcifying and non-calcifying cartilage was observed on the following two hydroxyapatite formation systems: (a) transformation of amorphous calcium phosphate to hydroxyapatite; (b) direct precipitation of hydroxyapatite from supersaturated calcium phosphate solutions. The aggregates were more effective inhibitors of apatite formation in both test systems, than equal weight solutions of subunits, but the subunit also delayed apatite formation. This suggests that in the epipryseal growth plate even the proteoglycan subunit must be removed by diffusion or enzyme cleavage for cartilage calcification to take place.

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