Dmp1Cre-directed knockdown of parathyroid hormone-related protein (PTHrP) in murine decidua is associated with a life-long increase in bone mass, width, and strength in male progeny

Niloufar Ansari; Tsuyoshi Isojima; Blessing Crimeen-Irwin; Ingrid J Poulton; Narelle E McGregor; Patricia WM Ho; Mark R Forwood; Christopher S Kovacs; Evdokia Dimitriadis; Jonathan H Gooi; T John Martin; Natalie A Sims

Journal article

Dmp1Cre-directed knockdown of parathyroid hormone-related protein (PTHrP) in murine decidua is associated with a life-long increase in bone mass, width, and strength in male progeny

Niloufar Ansari, Tsuyoshi Isojima, Blessing Crimeen-Irwin, Ingrid J Poulton, Narelle E McGregor, Patricia WM Ho, Mark R Forwood, Christopher S Kovacs, Evdokia Dimitriadis, Jonathan H Gooi, T John Martin, Natalie A Sims

JOURNAL OF BONE AND MINERAL RESEARCH | WILEY | Published : 2021

DOI: 10.1002/jbmr.4388

Abstract

Parathyroid hormone-related protein (PTHrP, gene name Pthlh) 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 heterozygous (flox/wild type) Dmp1Cre.Pthlhf/w parents, adult (16-week-old and 26-week-old) flox/flox (f/f) 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 greater bone size was observed in Dmp1Cre.Pthlhf/f(hom) mice as early as 12 days..

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University of Melbourne Researchers

Natalie Sims Author Medicine - St Vincent's Hospital

Jonathan Gooi Author Biochemistry and Pharmacology

Eva Dimitriadis Author Obstetrics and Gynaecology Royal Women's Hospital/Mercy

Grants

Funding Acknowledgements

This work was partially supported by National Health and Medical Research Council (Australia) Project Grants to Natalie A. Sims and T. John Martin. We thank the staff of the St. Vincent's Health Bioresources Centre for excellent animal care and assistance. Niloufar Ansari was supported by The University of Melbourne International Research Scholarship and a St. Vincent's Institute top-up scholarship. Tsuyoshi Isojima was supported by Travel Grants from Mochida Memorial Foundation for Medical and Pharmacological Research and The Foundation for Growth Science, Japan. Natalie A. Sims is supported by a National Health and Medical Research Council (Australia) Senior Research Fellowship, and was supported in 2018 by the SVI Brenda Shanahan Fellowship. St. Vincent's Institute is supported by the Victorian Government's Operational Infrastructure Support Programme.