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Dysplasia of the cementum, dentin, and alveolar bone has been proposed to be the main reasons for the exfoliation of teeth, while the extraordinarily complex intracellular mechanisms remain elusive. Dental pulp stem cells (DPSCs) have been demonstrated to successfully regenerate functional pulp-dentin-like tissue. Dental pulp cells derived from HPP patients impaired mineralization; however, insight into the deeper mechanism is still unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The effects of ALPL on odontoblastic differentiation of DPSCs from HPP patient were assessed by Alizarin Red staining, immunofluorescent staining, Western blot and RT-PCR, and micro-CT assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      Here, we found DPSCs from HPP patient exhibited low ALP activity and impaired odontoblastic differentiation. Meanwhile, we found that loss of function of ALPL reduced phosphorylation of GSK3\u03b2 in DPSCs. While GSK3\u03b2 rephosphorylation improved odontoblastic differentiation of HPP DPSCs with LiCl treatment. Finally, we demonstrated systemic LiCl injection ameliorated tooth-associated defects in ALPL\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      mice by enhanced phosphorylation of GSK3\u03b2 in the teeth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study indicates that ALPL regulates odontoblastic differentiation of DPSCs and provides useful information for understanding how ALPL deficiency led to tooth dysplasia and, ultimately, may inform efforts at improvement tooth defects in HPP patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-021-02235-7","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T07:02:39Z","timestamp":1617692559000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["GSK3\u03b2 rephosphorylation rescues ALPL deficiency-induced impairment of odontoblastic differentiation of DPSCs"],"prefix":"10.1186","volume":"12","author":[{"given":"Liqiang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangdong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"2235_CR1","doi-asserted-by":"crossref","unstructured":"Beumer J 3rd, Trowbridge HO, Silverman S Jr, Eisenberg E. Childhood hypophosphatasia and the premature loss of teeth. Oral Surg Oral Med Oral Pathol. 1973;35:631\u201340.","DOI":"10.1016\/0030-4220(73)90028-5"},{"key":"2235_CR2","doi-asserted-by":"crossref","unstructured":"Haliloglu B, Guran T, Atay Z, Abali S, Mornet E, Bereket A, et al. Infantile loss of teeth: odontohypophosphatasia or childhood hypophosphatasia. Eur J Pediatr. 2013;172:851\u20133.","DOI":"10.1007\/s00431-012-1868-4"},{"key":"2235_CR3","doi-asserted-by":"crossref","unstructured":"Simon S, Resch H, Klaushofer K, Roschger P, Zwerina J, Kocijan R. Hypophosphatasia: from diagnosis to treatment. Curr Rheumatol Rep. 2018;20:69.","DOI":"10.1007\/s11926-018-0778-5"},{"key":"2235_CR4","doi-asserted-by":"crossref","unstructured":"Rush ET. Childhood hypophosphatasia: to treat or not to treat. Orphanet J Rare Dis. 2018;13:116.","DOI":"10.1186\/s13023-018-0866-7"},{"key":"2235_CR5","doi-asserted-by":"crossref","unstructured":"Whyte MP. 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