{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T13:28:14Z","timestamp":1767014894621,"version":"3.48.0"},"reference-count":72,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical &amp;amp; Exp Dental Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      To explore the cellular behavior of stem cells derived from human exfoliated deciduous teeth (SHED) in response to inorganic pyrophosphate (PP\n                      <jats:sub>i<\/jats:sub>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      SHED cells were isolated from the dental pulp tissues of human primary exfoliated teeth. Cell proliferation was examined using the MTT assay, colony\u2010forming unit assay, and cell cycle analysis. Cell migration was evaluated using the scratch assay. Osteogenic differentiation was assessed by the expression of osteogenic marker genes and\n                      <jats:italic>in vitro<\/jats:italic>\n                      mineral deposition. Oil Red O staining was employed to determine intracellular lipid accumulation under adipogenic differentiation. For osteoclast differentiation, TRAP staining was used. The global gene expression profile was examined by RNA sequencing analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PP\n                      <jats:sub>i<\/jats:sub>\n                      reduced early cell apoptosis and enhanced cell migration. PP\n                      <jats:sub>i<\/jats:sub>\n                      inhibited mineral deposition dose\u2010dependently and significantly reduced\n                      <jats:italic>DSPP<\/jats:italic>\n                      and\n                      <jats:italic>BGLAP<\/jats:italic>\n                      expression. The higher dose of 10\u2009\u03bcM PP\n                      <jats:sub>i<\/jats:sub>\n                      decreased\n                      <jats:italic>RANKL<\/jats:italic>\n                      mRNA expression, while it did not influence\n                      <jats:italic>OPG<\/jats:italic>\n                      mRNA levels, resulting in the reduction of the\n                      <jats:italic>RANKL\/OPG<\/jats:italic>\n                      expression ratio. Culture medium from PP\n                      <jats:sub>i<\/jats:sub>\n                      \u2010treated SHED reduced the number of TRAP\u2010positive multinucleated cells. Further, PP\n                      <jats:sub>i<\/jats:sub>\n                      inhibited\n                      <jats:italic>CEBPA<\/jats:italic>\n                      but not\n                      <jats:italic>PPARG<\/jats:italic>\n                      and\n                      <jats:italic>LPL<\/jats:italic>\n                      mRNA expression under adipogenic induction. The intracellular lipid accumulation tended to decrease in PP\n                      <jats:sub>i<\/jats:sub>\n                      \u2010treated conditions (10 \u03bcM). The transcriptomic profiles illustrated that PP\n                      <jats:sub>i<\/jats:sub>\n                      potentially modulated several pathways, including the metabolism of lipids, interleukin\u20106, TGF\u2010\u03b21, and NOTCH signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      PP\n                      <jats:sub>i<\/jats:sub>\n                      inhibited osteo\/odontogenic, adipogenic and indirectly attenuated osteoclast differentiation by SHED. This study implicated that PP\n                      <jats:sub>i<\/jats:sub>\n                      can modulate the cellular responses of SHED.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cre2.70248","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T13:26:52Z","timestamp":1763645212000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyrophosphate Regulates Multilineage Differentiation in Stem Cells From Human Exfoliated Deciduous Teeth"],"prefix":"10.1002","volume":"11","author":[{"given":"Ravipha","family":"Suwittayarak","sequence":"first","affiliation":[{"name":"Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry Chulalongkorn University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5315-5565","authenticated-orcid":false,"given":"Nunthawan","family":"Nowwarote","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Faculty of Dentistry Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chatvadee","family":"Kornsuthisopon","sequence":"additional","affiliation":[{"name":"Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry Chulalongkorn University Bangkok Thailand"},{"name":"Department of Anatomy, Faculty of Dentistry Chulalongkorn University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waleerat","family":"Sukarawan","sequence":"additional","affiliation":[{"name":"Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry Chulalongkorn University Bangkok Thailand"},{"name":"Department of Paediatric Dentistry, Faculty of Dentistry Chulalongkorn University Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-0576","authenticated-orcid":false,"given":"Brian L.","family":"Foster","sequence":"additional","affiliation":[{"name":"Division of Biosciences, College of Dentistry The Ohio State University Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Egusa","sequence":"additional","affiliation":[{"name":"Division of Molecular and Regenerative Prosthodontics Tohoku University Graduate School of Dentistry Sendai Miyagi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1649-6357","authenticated-orcid":false,"given":"Thanaphum","family":"Osathanon","sequence":"additional","affiliation":[{"name":"Center of Excellence for Dental Stem Cell Biology, Faculty of Dentistry Chulalongkorn University Bangkok Thailand"},{"name":"Department of Oral Biology, Faculty of Dentistry Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","unstructured":"Abdelmagid S. 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