RegulatorsofBoneMineralization

Osteoblasts mineralize bone matrix by promoting hydroxyapatite crystal formation and growth in the interior of membrane-limited matrix vesicles (MVs) and by propagating the crystals onto the collagenous extracellular matrix. Two osteoblast proteins, tissue-nonspecific alkaline phosphatase (TNAP) and plasma cell membrane glycoprotein-1 (PC-1) are involved in this process. Schematic representation of the counterregulatory functions of TNAP and PC-1 in modulating extracellular PPi concentrations. (NTPs, nucleoside triphosphates). In the bone matrix, PC-1 is the major producer of PPi (thick arrows), which in turn has an inhibitory effect on hydroxyapatite deposition. TNAP has a positive influence on mineralization primarily by controlling the size of the inhibitory pool of PPi through its inorganic pyrophosphatase activity. TNAP also generates Pi by using NTPs and PPi as substrates, but other more major sources of Pi e.g., intestinal absorption, are likely to contribute the bulk of the Pi needed for hydroxyapatite deposition.

Contributor: Kosi Gramatikoff, PhD

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