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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 (<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>harpey's fibers) where they insert into tooth cementum and alveolar bone is also essential for the function of the tooth\u2010suspensory apparatus in occlusion and mastication. Molecular determinants of mineralization in these tissues include mineral ion concentrations (phosphate and calcium), pyrophosphate, small integrin\u2010binding ligand <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\u2010linked 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\u2010nonspecific alkaline phosphatase and phosphate\u2010regulating 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 <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010linked hypophosphatemia, respectively, where the levels of local and systemic circulating mineralization determinants are perturbed. In <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010linked hypophosphatemia, in addition to renal phosphate wasting causing low circulating phosphate levels, phosphorylated mineralization\u2010regulating small integrin\u2010binding ligand <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\u2010linked glycoproteins, such as matrix extracellular phosphoglycoprotein and osteopontin, and the phosphorylated peptides proteolytically released from them, such as the acidic serine\u2010 and aspartate\u2010rich\u2010motif peptide, may accumulate locally to impair mineralization in this disease.<\/jats:p>","DOI":"10.1111\/prd.12029","type":"journal-article","created":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T04:24:01Z","timestamp":1376281441000},"page":"102-122","source":"Crossref","is-referenced-by-count":69,"title":["Extracellular matrix mineralization in periodontal tissues: Noncollagenous matrix proteins, enzymes, and relationship to hypophosphatasia and X\u2010linked hypophosphatemia"],"prefix":"10.1111","volume":"63","author":[{"given":"Marc D.","family":"McKee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Hoac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William N.","family":"Addison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilana M. 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