{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T02:21:53Z","timestamp":1773714113372,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2023,3,12]],"date-time":"2023-03-12T00:00:00Z","timestamp":1678579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008918","name":"Jean Perkins Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008918","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The temporospatial equilibrium of phosphate contributes to physiological bone development and fracture healing, yet optimal control of phosphate content has not been explored in skeletal regenerative materials. Nanoparticulate mineralized collagen glycosaminoglycan (MC\u2010GAG) is a synthetic, tunable material that promotes in vivo skull regeneration. In this work, the effects of MC\u2010GAG phosphate content on the surrounding microenvironment and osteoprogenitor differentiation are investigated. This study finds that MC\u2010GAG exhibits a temporal relationship with soluble phosphate with elution early in culture shifting to absorption with or without differentiating primary bone marrow\u2010derived human mesenchymal stem cells (hMSCs). The intrinsic phosphate content of MC\u2010GAG is sufficient to stimulate osteogenic differentiation of hMSCs in basal growth media without the addition of exogenous phosphate in a manner that can be severely reduced, but not eliminated, by knockdown of the sodium phosphate transporters PiT\u20101 or PiT\u20102. The contributions of PiT\u20101 and PiT\u20102 to MC\u2010GAG\u2010mediated osteogenesis are nonredundant but also nonadditive, suggestive that the heterodimeric form is essential to its activity. These findings indicate that the mineral content of MC\u2010GAG alters phosphate concentrations within a local microenvironment resulting in osteogenic differentiation of progenitor cells via both PiT\u20101 and PiT\u20102.<\/jats:p>","DOI":"10.1002\/adhm.202202750","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T19:09:39Z","timestamp":1677784179000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Modulating Temporospatial Phosphate Equilibrium by Nanoparticulate Mineralized Collagen Materials Induces Osteogenesis via PiT\u20101 and PiT\u20102"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiaoyan","family":"Ren","sequence":"first","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery Department of Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Department of Orthopaedic Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Surgery and Perioperative Care Greater Los Angeles VA Healthcare System  Los Angeles CA 90073 USA"},{"name":"Molecular Biology Institute UCLA  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery Department of Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Department of Orthopaedic Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Surgery and Perioperative Care Greater Los Angeles VA Healthcare System  Los Angeles CA 90073 USA"},{"name":"Molecular Biology Institute UCLA  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiwand","family":"Bedar","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery Department of Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Department of Orthopaedic Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Surgery and Perioperative Care Greater Los Angeles VA Healthcare System  Los Angeles CA 90073 USA"},{"name":"Molecular Biology Institute UCLA  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Foulad","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery Department of Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Department of Orthopaedic Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Surgery and Perioperative Care Greater Los Angeles VA Healthcare System  Los Angeles CA 90073 USA"},{"name":"Molecular Biology Institute UCLA  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9092-5135","authenticated-orcid":false,"given":"Kelly X.","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery Department of Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Department of Orthopaedic Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Surgery and Perioperative Care Greater Los Angeles VA Healthcare System  Los Angeles CA 90073 USA"},{"name":"Molecular Biology Institute UCLA  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dillon","family":"Dejam","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery Department of Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Department of Orthopaedic Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Surgery and Perioperative Care Greater Los Angeles VA Healthcare System  Los Angeles CA 90073 USA"},{"name":"Molecular Biology Institute UCLA  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie J.","family":"Dahan","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery Department of Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Department of Orthopaedic Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Surgery and Perioperative Care Greater Los Angeles VA Healthcare System  Los Angeles CA 90073 USA"},{"name":"Molecular Biology Institute UCLA  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliki","family":"Kolliopoulos","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering Institute for Genomic Biology University of Illinois at Urbana\u2010Champaign  Urbana IL 61801 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan A.C.","family":"Harley","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering Institute for Genomic Biology University of Illinois at Urbana\u2010Champaign  Urbana IL 61801 USA"},{"name":"Department of Materials Science and Engineering Institute for Genomic Biology University of Illinois at Urbana\u2010Champaign  Urbana IL 61801 USA"},{"name":"Carl R. Woese Institute for Genomic Biology University of Illinois at Urbana\u2010Champaign  Urbana IL 61801 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-0837","authenticated-orcid":false,"given":"Justine C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery Department of Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Department of Orthopaedic Surgery UCLA David Geffen School of Medicine  Los Angeles CA 90095 USA"},{"name":"Surgery and Perioperative Care Greater Los Angeles VA Healthcare System  Los Angeles CA 90073 USA"},{"name":"Molecular Biology Institute UCLA  Los Angeles CA 90095 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201700232"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.01.059"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.02.020"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw4991"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.202000370"},{"key":"e_1_2_9_3_3","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202101467"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.2834"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201700641"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140021997"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10622"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(98)00151-3"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(00)00418-X"},{"key":"e_1_2_9_7_3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.15.7071"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321717111"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00104-07"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.344994"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.020603"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.106.132266"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.05.026"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.10.172"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.807339"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065979"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3691"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/jbm.a.32361","volume":"92","author":"Harley B. A.","year":"2010","journal-title":"J. Biomed. Mater. Res., Part A"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2013.07.016"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(96)81413-X"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470891315"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.08.006"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3609"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.071"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202202750","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202202750","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202202750","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T21:58:15Z","timestamp":1759787895000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202202750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,12]]},"references-count":30,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/adhm.202202750"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202202750","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,12]]},"assertion":[{"value":"2022-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2202750"}}