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Dent. Med"],"abstract":"<jats:p>Mineralization of the skeleton occurs by several physicochemical and biochemical processes and mechanisms that facilitate the deposition of hydroxyapatite (HA) in specific areas of the extracellular matrix (ECM). Two key phosphatases, phosphatase, orphan 1 (PHOSPHO1) and tissue-non-specific alkaline phosphatase (TNAP), play complementary roles in the mineralization process. The actions of PHOSPHO1 on phosphocholine and phosphoethanolamine in matrix vesicles (MVs) produce inorganic phosphate (P<jats:sub>i<\/jats:sub>) for the initiation of HA mineral formation within MVs. TNAP hydrolyzes adenosine triphosphate (ATP) and the mineralization inhibitor, inorganic pyrophosphate (PP<jats:sub>i<\/jats:sub>), to generate P<jats:sub>i<\/jats:sub> that is incorporated into MVs. Genetic mutations in the <jats:italic>ALPL<\/jats:italic> gene-encoding TNAP lead to hypophosphatasia (HPP), characterized by low circulating TNAP levels (ALP), rickets in children and\/or osteomalacia in adults, and a spectrum of dentoalveolar defects, the most prevalent being lack of acellular cementum leading to premature tooth loss. Given that the skeletal manifestations of genetic ablation of the <jats:italic>Phospho1<\/jats:italic> gene in mice resemble many of the manifestations of HPP, we propose that <jats:italic>Phospho1<\/jats:italic> gene mutations may underlie some cases of \u201cpseudo-HPP\u201d where ALP may be normal to subnormal, but <jats:italic>ALPL<\/jats:italic> mutation(s) have not been identified. The goal of this perspective article is to compare and contrast the loss-of-function effects of TNAP and PHOSPHO1 on the dentoalveolar complex to predict the likely dental phenotype in humans that may result from <jats:italic>PHOSPHO1<\/jats:italic> mutations. Potential cases of pseudo-HPP associated with <jats:italic>PHOSPHO1<\/jats:italic> mutations may resist diagnosis, and the dental manifestations could be a key criterion for consideration.<\/jats:p>","DOI":"10.3389\/fdmed.2022.826387","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T04:34:00Z","timestamp":1643862840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Perspective on Dentoalveolar Manifestations Resulting From PHOSPHO1 Loss-of-Function: A Form of Pseudohypophosphatasia?"],"prefix":"10.3389","volume":"3","author":[{"given":"Fatma F.","family":"Mohamed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Chavez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Amadeu de 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