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dc.contributor.authorAnsari, Niloufar
dc.contributor.authorIsojima, Tsuyoshi
dc.contributor.authorCrimeen-Irwin, Blessing
dc.contributor.authorPoulton, Ingrid J
dc.contributor.authorMcGregor, Narelle E
dc.contributor.authorHo, Patricia WM
dc.contributor.authorForwood, Mark R
dc.contributor.authorKovacs, Christopher S
dc.contributor.authorDimitriadis, Evdokia
dc.contributor.authorGooi, Jonathan H
dc.contributor.authorMartin, T John
dc.contributor.authorSims, Natalie A
dc.date.accessioned2021-06-18T01:19:23Z
dc.date.available2021-06-18T01:19:23Z
dc.date.issued2021
dc.identifier.issn0884-0431
dc.identifier.doi10.1002/jbmr.4388
dc.identifier.urihttp://hdl.handle.net/10072/405211
dc.description.abstractParathyroid hormone related-protein (PTHrP) is a pleiotropic regulator of tissue homeostasis. In bone, Dmp1Cre-targeted PTHrP deletion in osteocytes causes osteopenia and impaired cortical strength. We report here that this outcome depends on parental genotype. In contrast to our previous report using mice bred from Dmp1Cre.Phtlhf/w parents, adult (16 week old and 26 week old) Dmp1Cre.Pthlhf/f mice from homozygous parents (Dmp1Cre.Pthlhf/f(hom) ) have stronger bones, with 40% more trabecular bone mass and 30% greater femoral width than controls. This increase in bone size was observed as early as 12 days of age, when greater bone width was also found in male and female Dmp1Cre.Pthlhf/f(hom) mice, but not in gene-matched mice from heterozygous parents. This suggested a maternal influence on skeletal size prior to weaning. Although Dmp1Cre has previously been reported to cause gene recombination in mammary gland, milk PTHrP protein levels were normal. The wide-bone phenotype was also noted in utero: Dmp1Cre.Pthlhf/f(hom) embryonic femora were more mineralized and wider than controls. Closer examination revealed that Dmp1Cre caused PTHrP recombination in placenta, and in the maternal-derived decidual layer that resides between the placenta and the uterus. Decidua from mothers of Dmp1Cre.Pthlhf/f(hom) mice also exhibited lower PTHrP levels by immunohistochemistry and were smaller than controls. We conclude that Dmp1Cre leads to gene recombination in decidua, and that decidual PTHrP might, through an influence on decidual cells, limit embryonic bone radial growth. This suggests a maternal-derived developmental origin of adult bone strength.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherWiley
dc.relation.ispartofjournalJournal of Bone and Mineral Research
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchEngineering
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode09
dc.subject.fieldofresearchcode11
dc.subject.keywordsPTHrP
dc.subject.keywordsdevelopmental modeling
dc.subject.keywordsgenetic animal models
dc.subject.keywordsmolecular pathways - development
dc.titleDmp1Cre-directed knockdown of PTHrP in murine decidua is associated with a life-long increase in bone mass, width, and strength in male progeny
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationAnsari, N; Isojima, T; Crimeen-Irwin, B; Poulton, IJ; McGregor, NE; Ho, PWM; Forwood, MR; Kovacs, CS; Dimitriadis, E; Gooi, JH; Martin, TJ; Sims, NA, Dmp1Cre-directed knockdown of PTHrP in murine decidua is associated with a life-long increase in bone mass, width, and strength in male progeny, Journal of Bone and Mineral Research, 2021
dcterms.dateAccepted2021-06-02
dc.date.updated2021-06-17T22:33:47Z
dc.description.versionAccepted Manuscript (AM)
gro.rights.copyright© 2021 American Society for Bone and Mineral Research. This is the peer reviewed version of the following article: Dmp1Cre-directed knockdown of PTHrP in murine decidua is associated with a life-long increase in bone mass, width, and strength in male progeny, Journal of Bone and Mineral Research, 2021, which has been published in final form at https://publons.com/publon/10.1002/jbmr.4388. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html)
gro.hasfulltextFull Text
gro.griffith.authorForwood, Mark R.


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