As broadly demonstrated for the formation of a functional skeleton, proper mineralization of periodontal alveolar bone and teeth - where
calcium phosphate crystals are deposited and grow within an extracellular matrix - is essential for dental function. Mineralization defects in tooth dentin and cementum of the periodontium invariably lead to a weak (soft or brittle) dentition in which teeth become loose and prone to
infection and are lost prematurely. Mineralization of the extremities of periodontal ligament fibers (Sharpey's fibers) where they insert into tooth cementum and alveolar bone is also essential for the function of the tooth-suspensory apparatus in occlusion and mastication. Molecular determinants of mineralization in these tissues include
mineral ion concentrations (
phosphate and
calcium), pyrophosphate, small
integrin-binding
ligand N-linked
glycoproteins and matrix vesicles. Amongst the
enzymes important in regulating these mineralization determinants, two are discussed at length here, with clinical examples given, namely tissue-nonspecific
alkaline phosphatase and
phosphate-regulating gene with homologies to
endopeptidases on the X chromosome. Inactivating mutations in these
enzymes in humans and in mouse models lead to the soft bones and teeth characteristic of
hypophosphatasia and
X-linked hypophosphatemia, respectively, where the levels of local and systemic circulating mineralization determinants are perturbed. In
X-linked hypophosphatemia, in addition to renal
phosphate wasting causing low circulating
phosphate levels, phosphorylated mineralization-regulating small
integrin-binding
ligand N-linked
glycoproteins, such as matrix extracellular phosphoglycoprotein and
osteopontin, and the phosphorylated
peptides proteolytically released from them, such as the acidic
serine- and
aspartate-rich-motif
peptide, may accumulate locally to impair mineralization in this disease.