{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T13:40:21Z","timestamp":1777210821955,"version":"3.51.4"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T00:00:00Z","timestamp":1731715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008884","name":"Nakatani Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008884","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23KJ1234"],"award-info":[{"award-number":["JP23KJ1234"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H00659"],"award-info":[{"award-number":["JP20H00659"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003382","name":"Core Research for Evolutional Science and Technology","doi-asserted-by":"publisher","award":["JPMJCR22L5"],"award-info":[{"award-number":["JPMJCR22L5"]}],"id":[{"id":"10.13039\/501100003382","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biomech Model Mechanobiol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Secondary ossification and maintenance of the growth plate are crucial aspects of long bone formation. Parathyroid hormone-related protein (PTHrP) has been implicated as a key factor in maintaining the growth plate, and studies suggest that PTHrP expression in the resting zone is closely related with formation of the secondary ossification center (SOC). However, details of the relationship between resting zone PTHrP expression and preservation of the growth plate remain unclear. In this study, we aim to investigate the role of resting zone PTHrP expression on maintenance of the growth plate using a computational method. We extend an existing continuum-based particle model of tissue morphogenesis to include PTHrP and Indian hedgehog (Ihh) signaling, allowing the model to capture biochemical and mechanical regulation of individual cell activities. Our model indicates that the timing of resting zone PTHrP expression\u2014specifically the rate of increase in production at the onset of SOC formation\u2014is potentially a crucial mechanism for maintenance of the growth plate.<\/jats:p>","DOI":"10.1007\/s10237-024-01899-3","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T09:39:43Z","timestamp":1731749983000},"page":"125-137","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Timing of resting zone parathyroid hormone-related protein expression affects maintenance of the growth plate during secondary ossification: a computational study"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9850-6303","authenticated-orcid":false,"given":"Jorik","family":"Stoop","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-7028","authenticated-orcid":false,"given":"Yuka","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5280-4156","authenticated-orcid":false,"given":"Taiji","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,11,16]]},"reference":[{"key":"1899_CR1","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1242\/dev.129.8.1913","volume":"129","author":"J Alvarez","year":"2002","unstructured":"Alvarez J, Sohn P, Zeng X, Doetschman T, Robbins DJ, Serra R (2002) TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Development 129:1913\u20131924. https:\/\/doi.org\/10.1242\/dev.129.8.1913","journal-title":"Development"},{"key":"1899_CR2","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1359\/JBMR.050204","volume":"20","author":"J \u00c1lvarez","year":"2005","unstructured":"\u00c1lvarez J, Costales L, Serra R, Balb\u00edn M, L\u00f3pez JM (2005) Expression patterns of matrix metalloproteinases and vascular endothelial growth factor during epiphyseal ossification. J Bone Miner Res 20:1011\u20131021. https:\/\/doi.org\/10.1359\/JBMR.050204","journal-title":"J Bone Miner Res"},{"key":"1899_CR39","doi-asserted-by":"publisher","first-page":"477","DOI":"10.3970\/cmes.2004.005.477","volume":"5","author":"SG Bardenhagen","year":"2004","unstructured":"Bardenhagen SG, Kober EM (2004) The generalized interpolation material point method. CMES-Comp Model Eng Sci 5:477\u2013496.\u00a0https:\/\/doi.org\/10.3970\/cmes.2004.005.477","journal-title":"CMES-Comp Model Eng Sci"},{"key":"1899_CR3","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/s41390-019-0722-z","volume":"87","author":"AS Chagin","year":"2020","unstructured":"Chagin AS, Newton PT (2020) Postnatal skeletal growth is driven by the epiphyseal stem cell niche: potential implications to pediatrics. Pediatr Res 87:986\u2013990. https:\/\/doi.org\/10.1038\/s41390-019-0722-z","journal-title":"Pediatr Res"},{"key":"1899_CR4","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.bone.2007.07.020","volume":"41","author":"X Chen","year":"2007","unstructured":"Chen X, Macica C, Nasiri A, Judex S, Broadus AE (2007) Mechanical regulation of PTHrP expression in entheses. Bone 41:752\u2013759. https:\/\/doi.org\/10.1016\/j.bone.2007.07.020","journal-title":"Bone"},{"key":"1899_CR5","doi-asserted-by":"publisher","first-page":"3788","DOI":"10.1002\/art.23985","volume":"58","author":"X Chen","year":"2008","unstructured":"Chen X, Macica CM, Nasiri A, Broadus AE (2008) Regulation of articular chondrocyte proliferation and differentiation by Indian hedgehog and parathyroid hormone-related protein in mice. Arthritis Rheum 58:3788\u20133797. https:\/\/doi.org\/10.1002\/art.23985","journal-title":"Arthritis Rheum"},{"key":"1899_CR6","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/j.jmps.2017.12.011","volume":"112","author":"R de Rooij","year":"2018","unstructured":"de Rooij R, Kuhl E (2018) A physical multifield model predicts the development of volume and structure in the human brain. J Mech Phys Solids 112:563\u2013576. https:\/\/doi.org\/10.1016\/j.jmps.2017.12.011","journal-title":"J Mech Phys Solids"},{"key":"1899_CR7","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1159\/000109962","volume":"187","author":"CE Farnum","year":"2008","unstructured":"Farnum CE, Tinsley M, Hermanson JW (2008) Forelimb versus hindlimb skeletal development in the big brown bat, eptesicus fuscus: functional divergence is reflected in chondrocytic performance in autopodial growth plates. Cells Tissues Organs 187:35\u201347. https:\/\/doi.org\/10.1159\/000109962","journal-title":"Cells Tissues Organs"},{"key":"1899_CR8","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.compbiomed.2009.03.012","volume":"6","author":"DA Garz\u00f3n-Alvarado","year":"2009","unstructured":"Garz\u00f3n-Alvarado DA, Garc\u00eda-Aznar JM, Doblar\u00e9 M (2009) Appearance and location of secondary ossification centres may be explained by a reaction\u2013diffusion mechanism. Comput Biol Med 6:554\u2013561. https:\/\/doi.org\/10.1016\/j.compbiomed.2009.03.012","journal-title":"Comput Biol Med"},{"key":"1899_CR9","doi-asserted-by":"publisher","first-page":"6009","DOI":"10.3390\/ijms20236009","volume":"20","author":"SA Hallett","year":"2019","unstructured":"Hallett SA, Ono W, Ono N (2019) Growth plate chondrocytes: skeletal development, growth and beyond. Int J Mol Sci 20:6009. https:\/\/doi.org\/10.3390\/ijms20236009","journal-title":"Int J Mol Sci"},{"key":"1899_CR10","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","volume":"25","author":"L Hayflick","year":"1961","unstructured":"Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585\u2013621. https:\/\/doi.org\/10.1016\/0014-4827(61)90192-6","journal-title":"Exp Cell Res"},{"key":"1899_CR11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ydbio.2007.05.011","volume":"308","author":"MJ Hilton","year":"2007","unstructured":"Hilton MJ, Tu X, Long F (2007) Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage. Dev Biol 308:93\u2013105. https:\/\/doi.org\/10.1016\/j.ydbio.2007.05.011","journal-title":"Dev Biol"},{"key":"1899_CR12","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3970\/cmes.2005.008.119","volume":"8","author":"G Himpel","year":"2005","unstructured":"Himpel G, Kuhl E, Menzel A, Steinmann P (2005) Computational modelling of isotropic multiplicative growth. Comp Model Eng Sci 8:119\u2013134. https:\/\/doi.org\/10.3970\/cmes.2005.008.119","journal-title":"Comp Model Eng Sci"},{"key":"1899_CR13","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1073\/pnas.1005011108","volume":"108","author":"T Hirai","year":"2011","unstructured":"Hirai T, Chagin AS, Kobayashi T, Mackem S, Kronenberg HM (2011) Parathyroid hormone\/parathyroid hormone-related protein receptor signaling is required for maintenance of the growth plate in postnatal life. Proc Natl Acad Sci USA 108:191\u2013196. https:\/\/doi.org\/10.1073\/pnas.1005011108","journal-title":"Proc Natl Acad Sci USA"},{"key":"1899_CR14","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.ccr.2008.01.027","volume":"13","author":"H Kimura","year":"2008","unstructured":"Kimura H, Ng JM, Curran T (2008) Transient inhibition of the Hedgehog pathway in young mice causes permanent defects in bone structure. Cancer Cell 13:249\u2013260. https:\/\/doi.org\/10.1016\/j.ccr.2008.01.027","journal-title":"Cancer Cell"},{"key":"1899_CR15","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nature01657","volume":"423","author":"H Kronenberg","year":"2003","unstructured":"Kronenberg H (2003) Developmental regulation of the growth plate. Nature 423:332\u2013336. https:\/\/doi.org\/10.1038\/nature01657","journal-title":"Nature"},{"key":"1899_CR16","doi-asserted-by":"publisher","first-page":"418","DOI":"10.2214\/ajr.13.10711","volume":"202","author":"S Kwong","year":"2014","unstructured":"Kwong S, Kothary S, Poncinelli LL (2014) Skeletal development of the proximal humerus in the pediatric population: MRI features. Am J of Roentgenol 202:418\u2013425. https:\/\/doi.org\/10.2214\/ajr.13.10711","journal-title":"Am J of Roentgenol"},{"key":"1899_CR17","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1016\/j.bbagen.2016.06.010","volume":"1860","author":"Q Luo","year":"2016","unstructured":"Luo Q, Kuang D, Zhang B, Song G (2016) Cell stiffness determined by atomic force microscopy and its correlation with cell motility. Biochim Biophys Acta Gen Subj 1860:1953\u20131960. https:\/\/doi.org\/10.1016\/j.bbagen.2016.06.010","journal-title":"Biochim Biophys Acta Gen Subj"},{"key":"1899_CR18","doi-asserted-by":"publisher","first-page":"6382","DOI":"10.1073\/pnas.0608449104","volume":"104","author":"Y Maeda","year":"2007","unstructured":"Maeda Y, Nakamura E, Nguyen M-T, Suva LJ, Swain FL, Razzaque MS, Mackem S, Lanske B (2007) Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trabecular bone. Proc Natl Acad Sci USA 104:6382\u20136387. https:\/\/doi.org\/10.1073\/pnas.0608449104","journal-title":"Proc Natl Acad Sci USA"},{"key":"1899_CR19","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1242\/dev.018044","volume":"135","author":"KK Mak","year":"2008","unstructured":"Mak KK, Kronenberg HM, Chaung P-T, Mackem S, Yang Y (2008) Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy. Development 135:1947\u20131956. https:\/\/doi.org\/10.1242\/dev.018044","journal-title":"Development"},{"key":"1899_CR20","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/s1534-5807(02)00261-7","volume":"3","author":"E Minina","year":"2002","unstructured":"Minina E, Kreschel C, Naski MC, Ornitz DM, Vortkamp A (2002) Interaction of FGF, Ihh\/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Dev Cell 3:439\u2013449. https:\/\/doi.org\/10.1016\/s1534-5807(02)00261-7","journal-title":"Dev Cell"},{"key":"1899_CR21","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41586-018-0662-5","volume":"563","author":"K Mizuhashi","year":"2018","unstructured":"Mizuhashi K, Ono W, Matsushita Y, Sakagami N, Takahashi A, Saunders TL, Nagasawa T, Kronenberg HM, Ono N (2018) Resting zone of the growth plate houses a unique class of skeletal stem cells. Nature 563:254\u2013258. https:\/\/doi.org\/10.1038\/s41586-018-0662-5","journal-title":"Nature"},{"key":"1899_CR22","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41586-019-0989-6","volume":"567","author":"PT Newton","year":"2019","unstructured":"Newton PT, Li L, Zhou B et al (2019) A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate. Nature 567:234\u2013238. https:\/\/doi.org\/10.1038\/s41586-019-0989-6","journal-title":"Nature"},{"key":"1899_CR23","doi-asserted-by":"publisher","first-page":"6665","DOI":"10.3390\/ijms21186665","volume":"21","author":"S Ohba","year":"2020","unstructured":"Ohba S (2020) Hedgehog signaling in skeletal development: roles of Indian hedgehog and the mode of its action. Int J Mol Sci 21:6665. https:\/\/doi.org\/10.3390\/ijms21186665","journal-title":"Int J Mol Sci"},{"key":"1899_CR24","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jtbi.2011.07.011","volume":"287","author":"LM Peinado Cort\u00e9s","year":"2011","unstructured":"Peinado Cort\u00e9s LM, Vanegas Acosta JC, Garz\u00f3n Alvarado DA (2011) A mechanobiological model of epiphysis structures formation. J Theor Biol 287:13\u201325. https:\/\/doi.org\/10.1016\/j.jtbi.2011.07.011","journal-title":"J Theor Biol"},{"key":"1899_CR25","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1002\/jbm.1243","volume":"59","author":"RM Pidaparti","year":"2002","unstructured":"Pidaparti RM, Vogt A (2002) Experimental investigation of Poisson\u2019s ratio as a damage parameter for bone fatigue. J Biomed Mater Res 59:282\u2013287. https:\/\/doi.org\/10.1002\/jbm.1243","journal-title":"J Biomed Mater Res"},{"key":"1899_CR26","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.bbrc.2004.11.068","volume":"328","author":"S Provot","year":"2005","unstructured":"Provot S, Schipani E (2005) Molecular mechanisms of endochondral bone development. Biochem Biophys Res Commun 328:658\u2013665. https:\/\/doi.org\/10.1016\/j.bbrc.2004.11.068","journal-title":"Biochem Biophys Res Commun"},{"key":"1899_CR27","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1002\/ar.a.20268","volume":"288A","author":"PL Reno","year":"2006","unstructured":"Reno PL, Mcburney DL, Lovejoy CO, Horton WE Jr (2006) Ossification of the mouse metatarsal: differentiation and proliferation in the presence\/absence of a defined growth plate. The Anat Rec a: Discov in Mol Cell Evol Biol 288A:104\u2013118. https:\/\/doi.org\/10.1002\/ar.a.20268","journal-title":"The Anat Rec a: Discov in Mol Cell Evol Biol"},{"key":"1899_CR28","doi-asserted-by":"publisher","first-page":"116132","DOI":"10.1016\/j.bone.2021.116132","volume":"153","author":"SM Sadeghian","year":"2021","unstructured":"Sadeghian SM, Shapiro FD, Shefelbine SJ (2021) Computational model of endochondral ossification: Simulating growth of a long bone. Bone 153:116132. https:\/\/doi.org\/10.1016\/j.bone.2021.116132","journal-title":"Bone"},{"key":"1899_CR29","doi-asserted-by":"publisher","first-page":"803","DOI":"10.2217\/fon.12.76","volume":"8","author":"FN Soki","year":"2012","unstructured":"Soki FN, Park SI, McCauley LK (2012) The multifaceted actions of PTHrP in skeletal metastasis. Future Oncol 8:803\u2013817. https:\/\/doi.org\/10.2217\/fon.12.76","journal-title":"Future Oncol"},{"key":"1899_CR30","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/jor.1100170505","volume":"17","author":"SS Stevens","year":"1999","unstructured":"Stevens SS, Beaupr\u00e9 GS, Carter DR (1999) Computer model of endochondral growth and ossification in long bones: Biological and mechanobiological influences. J Orthop Res 17:646\u2013653. https:\/\/doi.org\/10.1002\/jor.1100170505","journal-title":"J Orthop Res"},{"key":"1899_CR31","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1007\/s10237-019-01222-5","volume":"19","author":"H Takeda","year":"2020","unstructured":"Takeda H, Kameo Y, Inoue Y, Adachi T (2020) An energy landscape approach to understanding variety and robustness in tissue morphogenesis. Biomech Model Mechanobiol 19:471\u2013479. https:\/\/doi.org\/10.1007\/s10237-019-01222-5","journal-title":"Biomech Model Mechanobiol"},{"key":"1899_CR32","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jbiomech.2004.11.006","volume":"39","author":"WR Trickey","year":"2006","unstructured":"Trickey WR, Baaijens FPT, Laursen TA, Alexopoulos LG, Guilak F (2006) Determination of the Poisson\u2019s ratio of the cell: recovery properties of chondrocytes after release from complete micropipette aspiration. J Biomech 39:78\u201387. https:\/\/doi.org\/10.1016\/j.jbiomech.2004.11.006","journal-title":"J Biomech"},{"key":"1899_CR33","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s10237-017-0997-0","volume":"17","author":"JJ Vaca-Gonz\u00e1lez","year":"2018","unstructured":"Vaca-Gonz\u00e1lez JJ, Moncayo-Donoso M, Guevara JM, Hata Y, Shefelbine SJ, Garz\u00f3n-Alvarado DA (2018) Mechanobiological modeling of endochondral ossification: an experimental and computational analysis. Biomech Model Mechanobiol 17:853\u2013875. https:\/\/doi.org\/10.1007\/s10237-017-0997-0","journal-title":"Biomech Model Mechanobiol"},{"key":"1899_CR34","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1210\/jc.2012-2142","volume":"97","author":"JJ Wysolmerski","year":"2012","unstructured":"Wysolmerski JJ (2012) Parathyroid hormone-related protein: an update. J Clin Endocrinol Metab 97:2947\u20132956. https:\/\/doi.org\/10.1210\/jc.2012-2142","journal-title":"J Clin Endocrinol Metab"},{"key":"1899_CR35","doi-asserted-by":"publisher","first-page":"e55212","DOI":"10.7554\/eLife.55212","volume":"9","author":"M Xie","year":"2020","unstructured":"Xie M, Gol\u2019din P, Herdina AN et al (2020) Secondary ossification center induces and protects growth plate structure. Elife 9:e55212. https:\/\/doi.org\/10.7554\/eLife.55212","journal-title":"Elife"},{"key":"1899_CR36","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1002\/nme.6598","volume":"122","author":"Y Yamaguchi","year":"2021","unstructured":"Yamaguchi Y, Moriguchi S, Terada K (2021) Extended B-spline-based implicit material point method. Int J Numer Methods Eng 122:1746\u20131769. https:\/\/doi.org\/10.1002\/nme.6598","journal-title":"Int J Numer Methods Eng"},{"key":"1899_CR37","doi-asserted-by":"publisher","first-page":"105828","DOI":"10.1016\/j.jmbbm.2023.105828","volume":"142","author":"Y Yokoyama","year":"2023","unstructured":"Yokoyama Y, Kameo Y, Adachi T (2023) Development of continuum-based particle models of cell growth and proliferation for simulating tissue morphogenesis. J Mech Behav Biomed Mater 142:105828. https:\/\/doi.org\/10.1016\/j.jmbbm.2023.105828","journal-title":"J Mech Behav Biomed Mater"},{"key":"1899_CR38","doi-asserted-by":"publisher","first-page":"117055","DOI":"10.1016\/j.bone.2024.117055","volume":"183","author":"Y Yokoyama","year":"2024","unstructured":"Yokoyama Y, Kameo Y, Sunaga J, Maki K, Adachi T (2024) Chondrocyte hypertrophy in the growth plate promotes stress anisotropy affecting long bone development through chondrocyte column formation. Bone 183:117055. https:\/\/doi.org\/10.1016\/j.bone.2024.117055","journal-title":"Bone"}],"container-title":["Biomechanics and Modeling in Mechanobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10237-024-01899-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10237-024-01899-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10237-024-01899-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T19:04:42Z","timestamp":1740251082000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10237-024-01899-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,16]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["1899"],"URL":"https:\/\/doi.org\/10.1007\/s10237-024-01899-3","relation":{},"ISSN":["1617-7959","1617-7940"],"issn-type":[{"value":"1617-7959","type":"print"},{"value":"1617-7940","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,16]]},"assertion":[{"value":"27 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no conflicts of interest to declare that are relevant to the content of this article.The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Mice experiments were approved by the Animal Experimentation Committee of Kyoto University (#Z19\u20132\u20134).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}