Journal article
Retinoic Acid Receptor γ Activity in Mesenchymal Stem Cells Regulates Endochondral Bone, Angiogenesis, and B Lymphopoiesis
AC Green, V Rudolph-Stringer, L Straszkowski, G Tjin, B Crimeen-Irwin, M Walia, TJ Martin, NA Sims, LE Purton
Journal of Bone and Mineral Research | WILEY | Published : 2018
DOI: 10.1002/jbmr.3558
Abstract
Retinoic acid receptor (RAR) signaling regulates bone structure and hematopoiesis through intrinsic and extrinsic mechanisms. This study aimed to establish how early in the osteoblast lineage loss of RARγ (Rarg) disrupts the bone marrow microenvironment. Bone structure was analyzed by micro–computed tomography (μCT) in Rarg–/– mice and mice with Rarg conditional deletion in Osterix-Cre–targeted osteoblast progenitors or Prrx1-Cre–targeted mesenchymal stem cells. Rarg–/– tibias exhibited less trabecular and cortical bone and impaired longitudinal and radial growth. The trabecular bone and longitudinal, but not radial, growth defects were recapitulated in Prrx1:RargΔ/Δ mice but not Osx1:RargΔ/..
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Funding Acknowledgements
This research was supported in part by a project grant from the National Health and Medical Research Council (NHMRC to LEP) and the Operational Infrastructure Support Program from the Victorian Government (to St. Vincent's Institute). LEP and NAS were supported by NHMRC Senior Research Fellowships. We thank the staff at the St Vincent's Bioresource Centre for caring for the animals used in this study; Ana Maluenda, Chacko Joseph, Diannita Kwang, Ingrid Poulton, and Narelle McGregor for excellent technical assistance; and Michael Thompson and Dijana Miljkovic in the SVI Flow Cytometry Facility for FACS-sorting cells for these studies. We thank Prof Pierre Chambon for providing us with the founders of the Rarg and Rarg<SUP>fl/fl</SUP> mice and Dr Andy McMahon for Osx1-Cre founder mice used in these studies.