{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:51:43Z","timestamp":1789055503367,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T00:00:00Z","timestamp":1734825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JST SPRING","award":["JPMJSP2017"],"award-info":[{"award-number":["JPMJSP2017"]}]},{"name":"Kyoto Prefectural Public University Corporation joint research","award":["JPMJSP2017"],"award-info":[{"award-number":["JPMJSP2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Mild hypophosphatasia (HPP) can be difficult to distinguish from other bone disorders in the absence of typical symptoms such as the premature loss of primary teeth. Therefore, this study aimed to analyze the crystallinity of hydroxyapatite (HAp) and the three-dimensional structure of collagen in HPP teeth at the molecular level and to search for new biomarkers of HPP. Raman spectroscopy was used to investigate the molecular structure, composition, and mechanical properties of primary teeth from healthy individuals and patients with HPP. The results showed that the crystallinity of HAp decreased and the carbonate apatite content increased in the region near the dentin\u2013enamel junction (DEJ) of HPP primary teeth. X-ray diffraction (XRD) analyses confirmed a decrease in HAp crystallinity near the DEJ, and micro-computed tomography (CT) scanning revealed a decrease in mineral density in this region. These results suggest incomplete calcification in HPP primary dentin and may contribute to the development of diagnostic and therapeutic agents.<\/jats:p>","DOI":"10.3390\/molecules29246049","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T10:06:52Z","timestamp":1734948412000},"page":"6049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Raman Spectroscopic Analysis of Molecular Structure and Mechanical Properties of Hypophosphatasia Primary Tooth"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6672-8465","authenticated-orcid":false,"given":"Hayata","family":"Imamura","sequence":"first","affiliation":[{"name":"Ceramic Physics Laboratory, Kyoto Institute of Technology, Sakyo-ku, Matsugasaki, Kyoto 606-8585, Japan"},{"name":"Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5224-7812","authenticated-orcid":false,"given":"Tetsuya","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan"},{"name":"Department of Dentistry, Kyoto Prefectural Rehabilitation Hospital for Mentally and Physically Disabled, Naka Ashihara, Joyo 610-0113, Japan"},{"name":"Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, 465 Kajii-cho, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-9714","authenticated-orcid":false,"given":"Wenliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Ceramic Physics Laboratory, Kyoto Institute of Technology, Sakyo-ku, Matsugasaki, Kyoto 606-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9797-1556","authenticated-orcid":false,"given":"Toshiro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narisato","family":"Kanamura","sequence":"additional","affiliation":[{"name":"Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-2783","authenticated-orcid":false,"given":"Hiroaki","family":"Onoda","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, Faculty of Science and Technology, Kyoto Prefectural University, 1-5, Shimogamo-nakaragi, Sakyo-ku, Kyoto 606-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Nakamura-Takahashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Tokyo Dental College, 2-9-18 Kandamisaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Tokyo Dental College, 2-9-18 Kandamisaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Nakada","sequence":"additional","affiliation":[{"name":"Toray Research Center, Inc., 2-11 Sonoyama 3-chome, Otsu 520-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pezzotti","sequence":"additional","affiliation":[{"name":"Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan"},{"name":"Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, 465 Kajii-cho, Kyoto 602-8566, Japan"},{"name":"Biomedical Engineering Center, Kansai Medical University, 1-9-11 Shin-machi, Hirakata, Osaka 573-1191, Japan"},{"name":"Department of Orthopedic Surgery, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan"},{"name":"Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy"},{"name":"Department of Molecular Science and Nanosystems, Ca\u2019 Foscari University of Venice, Via Torino 155, 30172 Venice, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1001\/archpedi.1948.02030020840003","article-title":"Hypophosphatasia: A New Developmental Anomaly","volume":"75","author":"Rathbun","year":"1948","journal-title":"Am. J. Dis. Child."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1750-1172-2-40","article-title":"Hypophosphatasia","volume":"2","author":"Mornet","year":"2007","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.bone.2017.02.011","article-title":"Hypophosphatasia: An Overview for 2017","volume":"102","author":"Whyte","year":"2017","journal-title":"Bone"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/S0022-3476(82)80061-9","article-title":"Infantile Hypophosphatasia: Enzyme Replacement Therapy by Intravenous Infusion of Alkaline Phosphatase-Rich Plasma from Patients with Paget Bone Disease","volume":"101","author":"Whyte","year":"1982","journal-title":"J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.bone.2019.05.036","article-title":"Recovery of Bone Mineralization and Quality During Asfotase Alfa Treatment in an Adult Patient with Infantile-Onset Hypophosphatasia","volume":"127","author":"Rolvien","year":"2019","journal-title":"Bone"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sekaran, S., Vimalraj, S., and Thangavelu, L. (2021). The physiological and pathological role of tissue nonspecific alkaline phosphatase beyond mineralization. Biomolecules, 11.","DOI":"10.3390\/biom11111564"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00198-020-05612-9","article-title":"Bone Mineral Density and Fracture Risk in Adult Patients with Hypophosphatasia","volume":"32","author":"Genest","year":"2021","journal-title":"Osteoporos. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s00431-008-0835-6","article-title":"Hypophosphatasia May Lead to Bone Fragility: Don\u2019t Miss It","volume":"168","author":"Moulin","year":"2009","journal-title":"Eur. J. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.berh.2007.11.003","article-title":"Hypophosphatasia","volume":"22","author":"Mornet","year":"2008","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.bone.2015.02.022","article-title":"Hypophosphatasia: Validation and Expansion of the Clinical Nosology for Children from 25 Years Experience with 173 Pediatric Patients","volume":"75","author":"Whyte","year":"2015","journal-title":"Bone"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bone.2016.08.019","article-title":"Hypophosphatasia: Natural History Study of 101 Affected Children Investigated at One Research Center","volume":"93","author":"Whyte","year":"2016","journal-title":"Bone"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s11914-016-0309-0","article-title":"Hypophosphatasia","volume":"14","author":"Linglart","year":"2016","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s00223-015-0079-1","article-title":"Alkaline Phosphatase and Hypophosphatasia","volume":"98","author":"Whyte","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.metabol.2017.08.013","article-title":"Hypophosphatasia","volume":"82","author":"Mornet","year":"2018","journal-title":"Metabolism"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1759720X19863997","DOI":"10.1177\/1759720X19863997","article-title":"Update on the Management of Hypophosphatasia","volume":"11","author":"Choida","year":"2019","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13023-019-1062-0","article-title":"Frequency and Age at Occurrence of Clinical Manifestations of Disease in Patients with Hypophosphatasia: A Systematic Literature Review","volume":"14","author":"Szabo","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_17","first-page":"e8594","article-title":"Hypophosphatasia: Current Literature for Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment","volume":"12","author":"Bangura","year":"2020","journal-title":"Cureus"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.33176\/AACB-19-00031","article-title":"Hypophosphatasia: Biological and Clinical Aspects, Avenues for Therapy","volume":"41","author":"Salles","year":"2020","journal-title":"Clin. Biochem. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tournis, S., Yavropoulou, M.P., Polyzos, S.A., and Doulgeraki, A. (2021). Hypophosphatasia. J. Clin. Med., 10.","DOI":"10.3390\/jcm10235676"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Villa-Su\u00e1rez, J.M., Garc\u00eda-Fontana, C., And\u00fajar-Vera, F., Gonz\u00e1lez-Salvatierra, S., de Haro-Mu\u00f1oz, T., Contreras-Bol\u00edvar, V., Garc\u00eda-Fontana, B., and Mu\u00f1oz-Torres, M. (2021). Hypophosphatasia: A Unique Disorder of Bone Mineralization. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094303"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00223-020-00676-5","article-title":"High-Level Expression of Alkaline Phosphatase by Adeno-Associated Virus Vector Ameliorates Pathological Bone Structure in a Hypophosphatasia Mouse Model","volume":"106","author":"Tanase","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Okawa, R., Nakamoto, T., Matayoshi, S., Nakano, K., and Kakimoto, N. (2022). Evaluation of Alveolar Bone Hypomineralization in Pediatric Hypophosphatasia Using Orthopantomography. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-05171-5"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jdsr.2022.06.002","article-title":"Dental Manifestation and Management of Hypophosphatasia","volume":"58","author":"Okawa","year":"2022","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1297\/cpe.29.9","article-title":"Clinical Practice Guidelines for Hypophosphatasia","volume":"29","author":"Michigami","year":"2020","journal-title":"Clin. Pediatr. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0917-2394(12)70266-5","article-title":"Oral Manifestations of Patients with Hypophosphatasia","volume":"22","author":"Okawa","year":"2012","journal-title":"Pediatr. Dent. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1365-263X.2012.01239.x","article-title":"Current Concepts in Hypophosphatasia: Case Report and Literature Review","volume":"23","author":"Hollis","year":"2013","journal-title":"Int. J. Paediatr. Dent."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/0030-4220(73)90028-5","article-title":"Childhood Hypophosphatasia and the Premature Loss of Teeth: A Clinical and Laboratory Study of Seven Cases","volume":"35","author":"Beumer","year":"1973","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0300-9785(73)80032-8","article-title":"Five Cases of Hypophosphatasia with Dental Findings","volume":"2","author":"Kjellman","year":"1973","journal-title":"Int. J. Oral Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/sj.bdj.2018.441","article-title":"Hypophosphatasia and the Importance of the General Dental Practitioner\u2013A Case Series and Discussion of Upcoming Treatments","volume":"224","author":"Feeney","year":"2018","journal-title":"Br. Dent. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1056\/NEJMoa1106173","article-title":"Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia","volume":"366","author":"Whyte","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1210\/jc.2015-3462","article-title":"Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia","volume":"101","author":"Whyte","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1007\/s00431-015-2641-2","article-title":"Lethal Hypophosphatasia Successfully Treated with Enzyme Replacement from Day 1 After Birth","volume":"175","author":"Okazaki","year":"2016","journal-title":"Eur. J. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e85971","DOI":"10.1172\/jci.insight.85971","article-title":"Asfotase Alfa Therapy for Children with Hypophosphatasia","volume":"1","author":"Whyte","year":"2016","journal-title":"JCI Insight"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"777","DOI":"10.2147\/TCRM.S87956","article-title":"Pathophysiology of Hypophosphatasia and the Potential Role of Asfotase Alfa","volume":"12","author":"Orimo","year":"2016","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1093\/jbmr\/zjae128","article-title":"Safety, Pharmacokinetics, and Pharmacodynamics of Efzimfotase Alfa, A Second-Generation Enzyme Replacement Therapy: Phase 1, Dose-Escalation Study in Adults with Hypophosphatasia","volume":"39","author":"Dahir","year":"2024","journal-title":"J. Bone Miner. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/cen.13343","article-title":"Safety and Efficacy of Treatment with Asfotase Alfa in Patients with Hypophosphatasia: Results from a Japanese Clinical Trial","volume":"87","author":"Kitaoka","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2017.07.010","article-title":"Monitoring Guidance for Patients with Hypophosphatasia Treated with Asfotase Alfa","volume":"122","author":"Kishnani","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1002\/jbmr.3075","article-title":"Hypophosphatasia: Enzyme Replacement Therapy Brings New Opportunities and New Challenges","volume":"32","author":"Whyte","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.2147\/DDDT.S154922","article-title":"Profile of Asfotase Alfa in the Treatment of Hypophosphatasia: Design, Development, and Place in Therapy","volume":"12","author":"Bowden","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00198-022-06597-3","article-title":"A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients","volume":"34","author":"Ng","year":"2023","journal-title":"Osteoporos. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s00198-020-05345-9","article-title":"Hypophosphatasia in Adolescents and Adults: Overview of Diagnosis and Treatment","volume":"31","author":"Bianchi","year":"2020","journal-title":"Osteoporos. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/jbmr.1565","article-title":"\u2018Atypical femoral fractures\u2019 During Bisphosphonate Exposure in Adult Hypophosphatasia","volume":"27","author":"Sutton","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jmbbm.2016.08.030","article-title":"Raman Spectroscopic Investigation on the Molecular Structure of Apatite and Collagen in Osteoporotic Cortical Bone","volume":"65","author":"Pezzotti","year":"2017","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1007\/s00216-015-8472-1","article-title":"Vibrational Algorithms for Quantitative Crystallographic Analyses of Hydroxyapatite-Based Biomaterials: I, Theoretical Foundations","volume":"407","author":"Pezzotti","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.bone.2014.04.030","article-title":"Mechanical and Mineral Properties of Osteogenesis Imperfecta Human Bones at the Tissue Level","volume":"65","author":"Imbert","year":"2014","journal-title":"Bone"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104787","DOI":"10.1016\/j.ejmg.2023.104787","article-title":"Prenatal Asfotase Alfa-Mediated Enzyme Replacement Therapy Restores Delayed Calcification in a Severe Infantile Form of Hypophosphatasia Model Mice","volume":"66","author":"Yoshida","year":"2023","journal-title":"Eur. J. Med. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sato, R., Maruyama, K., Nemoto, E., Sakisaka, Y., Suzuki, S., Li, J., Numazaki, K., Tada, H., and Yamada, S. (2022). Extracellular Vesicles Derived from Murine Cementoblasts Possess the Potential to Increase Receptor Activator of Nuclear Factor-\u03baB Ligand-Induced Osteoclastogenesis. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.825596"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1016\/j.jds.2024.02.025","article-title":"Cementocyte-Derived Extracellular Vesicles Regulate Osteoclastogenesis and Osteoblastogenesis","volume":"19","author":"Li","year":"2024","journal-title":"J. Dent. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1042\/bj3000723","article-title":"Modulation of crystal formation by bone phosphoproteins: Structural specificity of the osteopontin-mediated inhibition of hydroxyapatite formation","volume":"300","author":"Hunter","year":"1994","journal-title":"Biochem. J."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Jia, Q., Huang, Z., Wang, G., Sun, X., Wu, Y., Yang, B., Yang, T., Liu, J., Li, P., and Li, J. (2022). Osteopontin: An important protein in the formation of kidney stones. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1036423"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1359\/jbmr.060619","article-title":"Elevated skeletal osteopontin levels contribute to the hypophosphatasia phenotype in Akp2\u2212\/\u2212 mice","volume":"21","author":"Harmey","year":"2006","journal-title":"J. Bone Miner. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/(SICI)1097-0177(199703)208:3<432::AID-AJA13>3.0.CO;2-1","article-title":"Inactivation of two mouse alkaline phosphatase genes and establishment of a model of infantile hypophosphatasia","volume":"208","author":"Narisawa","year":"1997","journal-title":"Dev. Dyn."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1089\/hum.2010.210","article-title":"Rescue of severe infantile hypophosphatasia mice by AAV-mediated sustained expression of soluble alkaline phosphatase","volume":"22","author":"Matsumoto","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Moriishi, T., Ozasa, R., Ishimoto, T., Nakano, T., Hasegawa, T., Miyazaki, T., Liu, W., Fukuyama, R., Wang, Y., and Komori, H. (2020). Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass. PLOS Genet., 16.","DOI":"10.1371\/journal.pgen.1008586"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/24\/6049\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:58:04Z","timestamp":1760115484000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/24\/6049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,22]]},"references-count":54,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["molecules29246049"],"URL":"https:\/\/doi.org\/10.3390\/molecules29246049","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,22]]}}}