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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Solute Carrier Family 13 Member 5 (SLC13A5) encodes the sodium-dependent citrate cotransporter NaCT, which mediates citrate transport across cell membranes. Pathogenic variants in SLC13A5 cause developmental and epileptic encephalopathy 25 with amelogenesis imperfecta, DEE25; OMIM #615905, a debilitating autosomal recessive disorder. To better define the role of NaCT in ameloblast function and enamel mineralization, we used CRISPR\/Cas9 genome editing to generate Slc13a5R337* knock-in mice that terminate NaCT translation at the Arg337 codon, which is homologous to the human SLC13A5R333* variant associated with DEE25. We compared enamel phenotypes among wild-type, Slc13a5+\/+; heterozygous, Slc13a5+\/R337*; and homozygous, Slc13a5R337*\/R337* mice using light microscopy, in situ hybridization, immunohistochemistry, backscattered scanning electron microscopy (bSEM); and focused ion beam\u2013scanning electron microscopy (FIB-SEM) with quantitative imaging of organelles and matrix. Citrate bioassays were performed on serum, long bones, such as the femur and tibia, and developing mouse first molars, including enamel organ epithelium, mineralized tooth matrix, and pulp mesenchyme, to assess citrate levels during the presecretory, secretory, and maturation stages of enamel formation. In addition, first molars collected at postnatal days 0, 3, 5, and 12 were analyzed to characterize glycolytic and TCA cycle-related metabolic signatures. Homozygous Slc13a5R337*\/R337* mice exhibited severe defects during the secretory and maturation stages of amelogenesis. Most notably, Slc13a5R337*\/R337* ameloblasts failed to develop a Tomes\u2019 process, detached from the enamel matrix surface, and produced a thin, poorly mineralized crust on the dentin surface rather than organized enamel ribbons. Despite the absence of normal enamel deposition, ameloblasts initially appeared viable and did not become dysplastic until the late secretory stage. Cellular and subcellular analyses revealed increased secondary lysosomes and intracellular accumulation of enamel matrix proteins, consistent with impaired matrix processing or secretion. Citrate concentrations were elevated in serum and long bones at both 7 and 35 weeks of age. Citrate was elevated in secretory-stage Slc13a5R337*\/R337* molars at days 0 and 3, the enamel organ epithelium (including ameloblasts), the pulp mesenchyme (including odontoblasts), and mineralizing dentin and enamel matrices. These levels gradually declined at day 5 and into the enamel maturation stage (day 12). GC-MS-based analysis of central carbon metabolites revealed increased intracellular accumulation of citrate, malate, and pyruvate, suggesting altered energy metabolism and reduced metabolic efficiency in Slc13a5R337*\/R337* mice. Together, these findings indicate that loss of NaCT function in the ameloblasts causes citrate accumulation, which impairs hydroxyapatite formation. Consequently, only a thin, structurally defective mineral crust forms on the dentin surface, while mineral nodules develop ectopically within the maturation-stage enamel organ epithelium. We conclude that regulating citrate concentration is essential for proper appositional growth of enamel.<\/jats:p>","DOI":"10.3390\/ijms27167129","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:24:53Z","timestamp":1786353893000},"page":"7129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Citrate Transporter NaCT and Enamel Mineralization: The Slc13a5R337* Mouse Model"],"prefix":"10.3390","volume":"27","author":[{"given":"Charles E.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Anatomy & Cell Biology, Faculty of Medicine & Health Sciences, McGill University, Montreal, QC H3A 0C7, Canada"},{"name":"Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7192-6105","authenticated-orcid":false,"given":"James P.","family":"Simmer","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-7821","authenticated-orcid":false,"given":"Tian","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Orthodontic and Pediatric Dentistry, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6852-8790","authenticated-orcid":false,"given":"Yuanyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthodontic and Pediatric Dentistry, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4032-3619","authenticated-orcid":false,"given":"Olamide","family":"Animasahun","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Shankaran","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Chemical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Nagrath","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Chemical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4558-9026","authenticated-orcid":false,"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4055-0237","authenticated-orcid":false,"given":"Lauren E.","family":"Surface","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8071-469X","authenticated-orcid":false,"given":"Jie Ren Gerald","family":"Har","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, 1011 N University Ave., Ann Arbor, MI 48109, 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Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"310","DOI":"10.2119\/molmed.2016.00077","article-title":"Mutations in the Na+\/citrate cotransporter NaCT (SLC13A5) in pediatric patients with epilepsy and developmental delay","volume":"22","author":"Klotz","year":"2016","journal-title":"Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ajhg.2014.06.006","article-title":"Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life","volume":"95","author":"Thevenon","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Brown, T.L., Nye, K.L., and Porter, B.E. (2021). Growth and Overall Health of Patients with SLC13A5 Citrate Transporter Disorder. Metabolites, 11.","DOI":"10.3390\/metabo11110746"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wright, J.T. (2023). Enamel Phenotypes: Genetic and Environmental Determinants. Genes, 14.","DOI":"10.3390\/genes14030545"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1093\/brain\/awv263","article-title":"Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia","volume":"138","author":"Hardies","year":"2015","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Irizarry, A.R., Yan, G., Zeng, Q., Lucchesi, J., Hamang, M.J., Ma, Y.L., and Rong, J.X. (2017). Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175465"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liang, T., Hu, Y., Smith, C.E., Richardson, A.S., Zhang, H., Yang, J., Lin, B., Wang, S.K., Kim, J.W., and Chun, Y.H. (2019). AMBN mutations causing hypoplastic amelogenesis imperfecta and Ambn knockout-NLS-lacZ knockin mice exhibiting failed amelogenesis and Ambn tissue-specificity. Mol. Genet. Genom. Med., 7.","DOI":"10.1002\/mgg3.929"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/mgg3.253","article-title":"Ultrastructure of early amelogenesis in wild-type, Amelx-\/-, and Enam-\/- mice: Enamel ribbon initiation on dentin mineral and ribbon orientation by ameloblasts","volume":"4","author":"Smith","year":"2016","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Liang, T., Wang, S.K., Smith, C., Zhang, H., Hu, Y., Seymen, F., Koruyucu, M., Kasimoglu, Y., Kim, J.W., and Zhang, C. (2022). Enamel defects in Acp4(R110C\/R110C) mice and human ACP4 mutations. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-20684-9"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Simmer, J.P., Hu, J.C., Hu, Y., Zhang, S., Liang, T., Wang, S.K., Kim, J.W., Yamakoshi, Y., Chun, Y.H., and Bartlett, J.D. (2021). A genetic model for the secretory stage of dental enamel formation. J. Struct. Biol., 213.","DOI":"10.1016\/j.jsb.2021.107805"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Granchi, D., Baldini, N., Ulivieri, F.M., and Caudarella, R. (2019). Role of Citrate in Pathophysiology and Medical Management of Bone Diseases. Nutrients, 11.","DOI":"10.3390\/nu11112576"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Costello, L.C., Chellaiah, M., Zou, J., Franklin, R.B., and Reynolds, M.A. (2014). The status of citrate in the hydroxyapatite\/collagen complex of bone; and Its role in bone formation. J. Regen. Med. Tissue Eng., 3.","DOI":"10.7243\/2050-1218-3-4"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1515\/hsz-2013-0271","article-title":"Citrate\u2013new functions for an old metabolite","volume":"395","author":"Iacobazzi","year":"2014","journal-title":"Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"884","DOI":"10.2174\/1566524016666151123104855","article-title":"Extracellular Citrate in Health and Disease","volume":"15","author":"Mycielska","year":"2015","journal-title":"Curr. Mol. Med."},{"key":"ref_16","first-page":"1","article-title":"Evidence that Osteoblasts are Specialized Citrate-producing Cells that Provide the Citrate for Incorporation into the Structure of Bone","volume":"6","author":"Franklin","year":"2014","journal-title":"Open Bone J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5359","DOI":"10.1021\/acs.chemrev.0c00529","article-title":"Functional Distinction between Human and Mouse Sodium-Coupled Citrate Transporters and Its Biologic Significance: An Attempt for Structural Basis Using a Homology Modeling Approach","volume":"121","author":"Urbatsch","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jaramillo-Martinez, V., Sivaprakasam, S., Ganapathy, V., and Urbatsch, I.L. (2021). Drosophila INDY and Mammalian INDY: Major Differences in Transport Mechanism and Structural Features despite Mostly Similar Biological Functions. Metabolites, 11.","DOI":"10.3390\/metabo11100669"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41586-021-03230-x","article-title":"Structure and inhibition mechanism of the human citrate transporter NaCT","volume":"591","author":"Sauer","year":"2021","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.18689\/mjdl-1000120","article-title":"The Important Role and Implications of Citrate in the Composition, Structure, and Function of Oral\/Periodontal\/Craniofacial Tissues","volume":"3","author":"Costello","year":"2018","journal-title":"Madridge J. Dent. Oral Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22425","DOI":"10.1073\/pnas.1009219107","article-title":"Strongly bound citrate stabilizes the apatite nanocrystals in bone","volume":"107","author":"Hu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1002\/jbmr.60","article-title":"Progressive ankylosis protein (ANK) in osteoblasts and osteoclasts controls bone formation and bone remodeling","volume":"25","author":"Kim","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Szeri, F., Lundkvist, S., Donnelly, S., Engelke, U.F.H., Rhee, K., Williams, C.J., Sundberg, J.P., Wevers, R.A., Tomlinson, R.E., and Jansen, R.S. (2020). The membrane protein ANKH is crucial for bone mechanical performance by mediating cellular export of citrate and ATP. PLoS Genet., 16.","DOI":"10.1371\/journal.pgen.1008884"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1086\/509881","article-title":"Biochemical and genetic analysis of ANK in arthritis and bone disease","volume":"79","author":"Gurley","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1161\/CIRCRESAHA.124.325152","article-title":"ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm","volume":"135","author":"Wu","year":"2024","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hu, J.C., Liang, T., Zhang, H., Hu, Y., Yamakoshi, Y., Yamamoto, R., Zhang, C., Li, H., Smith, C.E., and Simmer, J.P. (2025). Citrate Transporter Expression and Localization: The Slc13a5(Flag) Mouse Model. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26146707"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/(SICI)1097-0185(199803)250:3<268::AID-AR2>3.0.CO;2-X","article-title":"Crown morphology, enamel distribution, and enamel structure in mouse molars","volume":"250","author":"Lyngstadaas","year":"1998","journal-title":"Anat. Rec."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dirckx, N., Zhang, Q., Chu, E.Y., Tower, R.J., Li, Z., Guo, S., Yuan, S., Khare, P.A., Zhang, C., and Verardo, A. (2022). A specialized metabolic pathway partitions citrate in hydroxyapatite to impact mineralization of bones and teeth. Proc. Natl. Acad. Sci. USA, 119.","DOI":"10.1073\/pnas.2212178119"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ye, Z., Wang, S., Zhang, C., and Zhao, Y. (2020). Coordinated Modulation of Energy Metabolism and Inflammation by Branched-Chain Amino Acids and Fatty Acids. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00617"},{"key":"ref_30","unstructured":"(1996). The Third Carolina Conference on Tooth Enamel Formation. Chapel Hill, North Carolina, October 18-20, 1995. Conference Proceedings. Adv. Dent. Res., 10, 89\u2013275."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Liang, T., Hu, Y., Kawasaki, K., Zhang, H., Zhang, C., Saunders, T.L., Simmer, J.P., and Hu, J.C. (2021). Odontogenesis-associated phosphoprotein truncation blocks ameloblast transition into maturation in Odaph(C41*\/C41*) mice. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-80912-y"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Li, Z., and Wang, H. (2021). Molecular Mechanisms of the SLC13A5 Gene Transcription. Metabolites, 11.","DOI":"10.3390\/metabo11100706"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zara, V., Assalve, G., and Ferramosca, A. (2022). Multiple roles played by the mitochondrial citrate carrier in cellular metabolism and physiology. Cell. Mol. Life Sci., 79.","DOI":"10.1007\/s00018-022-04466-0"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kumar, A., Cordes, T., Thalacker-Mercer, A.E., Pajor, A.M., Murphy, A.N., and Metallo, C.M. (2021). NaCT\/SLC13A5 facilitates citrate import and metabolism under nutrient-limited conditions. Cell Rep., 36.","DOI":"10.1016\/j.celrep.2021.109701"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5993","DOI":"10.1016\/S0021-9258(18)62653-5","article-title":"Citrate and the conversion of carbohydrate into fat. Fatty acid synthesis by a combination of cytoplasm and mitochondria","volume":"245","author":"Watson","year":"1970","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zahn, G., Baukmann, H.A., Wu, J., Jordan, J., Birkenfeld, A.L., Dirckx, N., and Schmidt, M.F. (2023). Targeting Longevity Gene SLC13A5: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis. Metabolites, 13.","DOI":"10.3390\/metabo13121186"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8714","DOI":"10.1021\/acs.jafc.1c03105","article-title":"Regulation on Citrate Influx and Metabolism through Inhibiting SLC13A5 and ACLY: A Novel Mechanism Mediating the Therapeutic Effects of Curcumin on NAFLD","volume":"69","author":"Sun","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jimenez-Armijo, A., Morkmued, S., Ahumada, J.T., Kharouf, N., de Feraudy, Y., Gogl, G., Riet, F., Niederreither, K., Laporte, J., and Birling, M.C. (2024). The Rogdi knockout mouse is a model for Kohlschutter-Tonz syndrome. Sci. Rep., 14.","DOI":"10.1038\/s41598-023-50870-2"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bartlett, J.D., Smith, C.E., Hu, Y., Ikeda, A., Strauss, M., Liang, T., Hsu, Y.H., Trout, A.H., McComb, D.W., and Freeman, R.C. (2021). MMP20-generated amelogenin cleavage products prevent formation of fan-shaped enamel malformations. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-90005-z"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.cell.2016.05.053","article-title":"Leveraging Rules of Nonsense-Mediated mRNA Decay for Genome Engineering and Personalized Medicine","volume":"165","author":"Popp","year":"2016","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Liang, T., Smith, C.E., Hu, Y., Zhang, H., Zhang, C., Xu, Q., Lu, Y., Qi, L., Hu, J.C., and Simmer, J.P. (2023). Dentin defects caused by a Dspp(-1) frameshift mutation are associated with the activation of autophagy. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-33362-1"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/mgg3.143","article-title":"Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation","volume":"3","author":"Wang","year":"2015","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hu, J., Hu, Y., Lu, Y., Smith, C., Lertlam, R., Wright, J., Suggs, C., McKee, M., Beniash, E., and Kabir, M. (2014). Enamelin Is Critical for Ameloblast Integrity and Enamel Ultrastructure Formation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089303"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: A novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"Wang","year":"2012","journal-title":"J. Mol. Diagn."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.matbio.2015.11.007","article-title":"Maturation stage enamel malformations in Amtn and Klk4 null mice","volume":"52\u201354","author":"Nunez","year":"2016","journal-title":"Matrix Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0003-9969(91)90090-H","article-title":"Cyclical changes in pH in bovine developing enamel as sequential bands","volume":"36","author":"Sasaki","year":"1991","journal-title":"Arch. Oral Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1177\/0022034514564186","article-title":"Amelogenins as potential buffers during secretory-stage amelogenesis","volume":"94","author":"Guo","year":"2015","journal-title":"J. Dent. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7129\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T04:24:42Z","timestamp":1786422282000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7129"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,9]]},"references-count":47,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167129"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167129","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,9]]}}}