Protein kinase D3 conditional knockout impairs osteoclast formation and increases trabecular bone volume in male mice

Samuel D. Burciaga, Flavia Saavedra, Lori Fischer, Karen Johnstone, Eric D. Jensen

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Studies using kinase inhibitors have shown that the protein kinase D (PRKD) family of serine/threonine kinases are required for formation and function of osteoclasts in culture. However, the involvement of individual protein kinase D genes and their in vivo significance to skeletal dynamics remains unclear. In the current study we present data indicating that protein kinase D3 is the primary form of PRKD expressed in osteoclasts. We hypothesized that loss of PRKD3 would impair osteoclast formation, thereby decreasing bone resorption and increasing bone mass. Conditional knockout (cKO) of Prkd3 using a murine Cre/Lox system driven by cFms-Cre revealed that its loss in osteoclast-lineage cells reduced osteoclast differentiation and resorptive function in culture. Examination of the Prkd3 cKO mice showed that bone parameters were unaffected in the femur at 4 weeks of age, but consistent with our hypothesis, Prkd3 conditional knockout resulted in 18 % increased trabecular bone mass in male mice at 12 weeks and a similar increase at 6 months. These effects were not observed in female mice. As a further test of our hypothesis, we asked if Prkd3 cKO could protect against bone loss in a ligature-induced periodontal disease model but did not see any reduction in bone destruction in this system. Together, our data indicate that PRKD3 promotes osteoclastogenesis both in vitro and in vivo.

Original languageEnglish (US)
Article number116759
StatePublished - Jul 2023

Bibliographical note

Funding Information:
This work was supported by funds provided through the University of Minnesota School of Dentistry to EDJ.

Publisher Copyright:
© 2023 Elsevier Inc.


  • Bone remodeling
  • Bone resorption
  • Osteoclast differentiation
  • Protein kinase D

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't


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