Hdac3 deletion in myeloid progenitor cells enhances bone healing in females and limits osteoclast fusion via Pmepa1

David H.H. Molstad, Elizabeth Zars, Andrew Norton, Kim C. Mansky, Jennifer J. Westendorf, Elizabeth W. Bradley

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5 Scopus citations


Previous studies examining the role of the histone deacetylase Hdac3 within myeloid cells demonstrated that Hdac3 promotes M2 activation and tissue healing in inflammatory conditions. Since myeloid lineage cells are required for proper bone formation and regeneration, in this study we examined the functions of Hdac3 during bone healing. Conditional deletion of Hdac3 within myeloid progenitors accelerates healing of cortical bone defects. Moreover, reduced osteoclast numbers within the defect site are correlated with Hdac3 suppression. Ex vivo osteoclastogenesis assays further demonstrate that Hdac3 deficiency limits osteoclastogenesis, the number of nuclei per cell and bone resorption, suggesting a defect in cell fusion. High throughput RNA sequencing identified the transmembrane protein Pmepa1 as a differentially expressed gene within osteoclast progenitor cells. Knockdown of Pmepa1 partially restores defects in osteoclastogenesis induced by Hdac3 deficiency. These results show that Hdac3 is required for optimal bone healing and osteoclast fusion, potentially via its regulation of Pmepa1 expression.

Original languageEnglish (US)
Article number21804
JournalScientific reports
Issue number1
StatePublished - Dec 11 2020

Bibliographical note

Funding Information:
This work was made possible by research grants from the National Institutes of Health (AR065397, AR072634, AR068103, AR065402, and AR067129), the Mayo Clinic Center for Biomedical Discovery, the Mayo Clinic Foundation, and the University of Minnesota Stem Cell Institute and Board of Regents. These contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2020, The Author(s).


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