Stage- and tissue-specific effect of cyclophosphamide during tooth development

Nakatsugawa, Kohei; Kurosaka, Hiroshi; Inubushi, Toshihiro; Aoyama, Gozo; Isogai, Yukako; Usami, Yu; Toyosawa, Satoru; Yamashiro, Takashi

doi:https://doi.org/10.1093/ejo/cjz002

Stage- and tissue-specific effect of cyclophosphamide during tooth development

Nakatsugawa, Kohei; Kurosaka, Hiroshi; Inubushi, Toshihiro et al.

European Journal of Orthodontics, 2019, 41(5), 519-530

アクセス数:111件（2026-02-17 15:43 集計）

固定URL: https://hdl.handle.net/11094/103599

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タイトル	Stage- and tissue-specific effect of cyclophosphamide during tooth development
著者	NRID 1000040848248 1000040848248 researchmap permalink NakatsugawaK NakatsugawaK Scopus Author ID 57201396219 57201396219 著者名 Nakatsugawa, Kohei
	NRID 1000020509369 1000020509369 ORCID 0000-0002-8956-5467 0000-0002-8956-5467 researchmap permalink kurosakahiroshi kurosakahiroshi Scopus Author ID 11839162500 11839162500 著者名 Kurosaka, Hiroshi
	NRID 1000030550941 1000030550941 ORCID 0000-0001-5303-4763 0000-0001-5303-4763 researchmap permalink opathone0141 opathone0141 Scopus Author ID 23097933700 23097933700 著者名 Inubushi, Toshihiro
	NRID 1000000838542 1000000838542 researchmap permalink aoyamagozo aoyamagozo Scopus Author ID 57209970565 57209970565 著者名 Aoyama, Gozo
	NRID 1000020724743 1000020724743 著者名 Isogai, Yukako
	NRID 1000080444579 1000080444579 ORCID 0000-0003-4816-2132 0000-0003-4816-2132 researchmap permalink yuusami yuusami Scopus Author ID 55263165500 55263165500 著者名 Usami, Yu
	NRID 1000030243249 1000030243249 ORCID 0000-0002-0338-0251 0000-0002-0338-0251 researchmap permalink osteobone0729 osteobone0729 Scopus Author ID 7003411866 7003411866 著者名 Toyosawa, Satoru
	NRID 1000070294428 1000070294428 ORCID 0000-0002-4419-9643 0000-0002-4419-9643 researchmap permalink read0051793 read0051793 Scopus Author ID 55416765600 55416765600 著者名 Yamashiro, Takashi
内容	This is a pre-copyedited, author-produced version of an article accepted for publication in European Journal of Orthodontics following peer review. The version of record Nakatsugawa K., Kurosaka H., Inubushi T., et al. Stage- and tissue-specific effect of cyclophosphamide during tooth development. European Journal of Orthodontics 41(5), pp. 519-530 (2019) is available online at: https://doi.org/10.1093/ejo/cjz002.
抄録	Objective: The aim of this study was to investigate the toxic effect of cyclophosphamide (CPA) in the development of rodent molars. Methods: CPA was administered intraperitoneally in postnatal mice between Day 1 and Day 10, and the morphological phenotype was evaluated at Day 26 using micro-computed tomography and histological analysis, including cell proliferation and cell death analyses. Results: M3 molars of the mice who received 100 mg/kg CPA treatment at Day 6 or M2 molars who received treatment at Day 1 resulted in tooth agenesis or marked hypoplasia. Histological observation demonstrated that CPA treatment at Day 6 resulted in shrinkage of the M3 tooth germs, with a significant reduction in the proliferation of apoptotic cells. Conversely, CPA exposure at Day 2, which occurs at around the bud stage of M3, resulted in crown and root hypoplasia, with reduced numbers of cusp and root. In addition, CPA exposure at Day 10, which is the late bell stage of M3, induced root shortening; however, it did not affect crown morphogenesis. Limitations: The timing of CPA administration is limited to after birth.Therefore, its effect during the early stages of M1 and M2 could not be investigated. Conclusion: Defective phenotypes were evident in both crown and roots due to the effect of CPA. Interestingly, the severity of the phenotypes was associated with the developmental stages of the tooth germs at the time of CPA administration.The cap/early bell stage is the most susceptive timing for tooth agenesis, whereas the late bell stage is predominantly affected in terms of root formation by CPA administration.
出版者	Oxford University Press
収録物名	European Journal of Orthodontics
巻(号)	41(5)
ページ	519-530
刊行年月	2019-02-02
言語	英語
ハンドルURL	https://hdl.handle.net/11094/103599
PISSN	01415387
eISSN	14602210
関連情報 (isVersionOf)	DOI (出版社版) https://doi.org/10.1093/ejo/cjz002
関連情報 (isPartOf)	DOI (出版社版) https://doi.org/10.18910/72255
アクセス権	open access
出版タイプ	Accepted Manuscript
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	European Journal of Orthodontics. 2019, 41(5), p. 519-530
DC.title	Stage- and tissue-specific effect of cyclophosphamide during tooth development
DC.creator	Nakatsugawa, Kohei
	Kurosaka, Hiroshi
	Inubushi, Toshihiro
	Aoyama, Gozo
	Isogai, Yukako
	Usami, Yu
	Toyosawa, Satoru
	Yamashiro, Takashi
DC.publisher	Oxford University Press
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2019-02-02
DC.identifier	https://doi.org/10.1093/ejo/cjz002
DC.identifier	https://doi.org/10.18910/72255
DC.description	This is a pre-copyedited, author-produced version of an article accepted for publication in European Journal of Orthodontics following peer review. The version of record Nakatsugawa K., Kurosaka H., Inubushi T., et al. Stage- and tissue-specific effect of cyclophosphamide during tooth development. European Journal of Orthodontics 41(5), pp. 519-530 (2019) is available online at: https://doi.org/10.1093/ejo/cjz002.
DCTERMS.abstract	Objective: The aim of this study was to investigate the toxic effect of cyclophosphamide (CPA) in the development of rodent molars. Methods: CPA was administered intraperitoneally in postnatal mice between Day 1 and Day 10, and the morphological phenotype was evaluated at Day 26 using micro-computed tomography and histological analysis, including cell proliferation and cell death analyses. Results: M3 molars of the mice who received 100 mg/kg CPA treatment at Day 6 or M2 molars who received treatment at Day 1 resulted in tooth agenesis or marked hypoplasia. Histological observation demonstrated that CPA treatment at Day 6 resulted in shrinkage of the M3 tooth germs, with a significant reduction in the proliferation of apoptotic cells. Conversely, CPA exposure at Day 2, which occurs at around the bud stage of M3, resulted in crown and root hypoplasia, with reduced numbers of cusp and root. In addition, CPA exposure at Day 10, which is the late bell stage of M3, induced root shortening; however, it did not affect crown morphogenesis. Limitations: The timing of CPA administration is limited to after birth.Therefore, its effect during the early stages of M1 and M2 could not be investigated. Conclusion: Defective phenotypes were evident in both crown and roots due to the effect of CPA. Interestingly, the severity of the phenotypes was associated with the developmental stages of the tooth germs at the time of CPA administration.The cap/early bell stage is the most susceptive timing for tooth agenesis, whereas the late bell stage is predominantly affected in terms of root formation by CPA administration.
DC.format	103599
citation_title	Stage- and tissue-specific effect of cyclophosphamide during tooth development
citation_author	Nakatsugawa, Kohei
	Kurosaka, Hiroshi
	Inubushi, Toshihiro
	Aoyama, Gozo
	Isogai, Yukako
	Usami, Yu
	Toyosawa, Satoru
	Yamashiro, Takashi
citation_publisher	Oxford University Press
citation_language	英語
citation_date	2019-02-02
citation_journal_title	European Journal of Orthodontics
citation_volume	41
citation_issue	5
citation_firstpage	519
citation_lastpage	530
citation_doi	https://doi.org/10.1093/ejo/cjz002
citation_doi	https://doi.org/10.18910/72255
citation_public_url	https://hdl.handle.net/11094/103599

Stage- and tissue-specific effect of cyclophosphamide during tooth development

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