Biomedical Engineering Reference
In-Depth Information
Fig. 4.1
Proposed function of DMP1. DMP1 self-assembles to the oligomeric state and inhibits
spontaneous precipitation by sequestering calcium phosphate clusters from external solution.
Binding of the protein to collagen fibers promotes nucleation of apatite in the matrix. Reprinted
with permission from [
40
]. (Copyright 2005, American Chemical Society)
In addition to hard tissues such as bone and teeth, body fluids including saliva,
milk, and urine are supersaturated with respect to HAP. When calcification occurs in
blood vessels, it causes arteriosclerosis. Therefore, a mechanism to prevent calcium
phosphate deposition in body fluid is needed for soft tissues. Fetuin forms a complex
with calcium phosphate, which prevents mineral deposition [
42
,
43
]. In milk, casein
and osteopontin form a complex with calcium phosphate and further form micelles,
resulting in prevention of mineral deposition in serum. In vitro experiments using a
phosphorylated form of a 25 amino acid peptide, derived from the casein sequence,
showed that ACP clusters with a radius of 2.4 nm were covered by peptide molecules
with a thickness of 1.6 nm [
44
,
45
]. A phosphorylated form of an osteopontin-
derived peptide also binds to ACP clusters, forming a complex that prevents calcium
phosphate precipitation [
46
].
In some cases, deposition of ACP is promoted. Poly-lysine and poly-glutamic
acid (basic and acidic polymers with an isoelectric point (p
I
) of 10.5 and 4.9,
respectively) were added to a calcium phosphate solution supersaturated with
respect to ACP. Deposition of ACP was accelerated at a low concentration of either
polymer, and deposition was delayed at a high concentration. Although the detailed
molecular mechanisms of this acceleration and inhibition is are unknown, it was
found that, regardless of negative or positive charge, mineral deposition is either
accelerated or inhibited in a dose-dependent manner regardless of the polymer's
charge [
47
].
