Osteocyte apoptosis is required for production of osteoclastogenic signals following bone fatigue in vivo

Oran D. Kennedy, Damien M. Laudier, Robert J. Majeska, Hui B. Sun, Mitchell B. Schaffler

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Osteocyte apoptosis is spatially, temporally and functionally linked to the removal and replacement of microdamage in the bone. Recently we showed that microdamage elicits distinct responses in two populations of osteocytes near the injury site. Osteocytes directly adjacent to microdamage undergo apoptosis, whereas there is a second group of osteocytes located adjacent to the apoptotic population that upregulate expression of osteoclastogenic signaling molecules. In this study we used the pan-caspase inhibitor QVD to test the hypothesis that osteocyte apoptosis is an obligatory step in the production of key osteoclastogenic signals by in situ osteocytes in fatigue-damaged bone. We found, based on real-time PCR and immunohistochemistry assays, that expression of the apoptosis marker caspase-3 as well osteoclastogenic proteins RANKL and VEGF were increased following fatigue, while expression of the RANKL antagonist OPG decreased. However, when apoptosis was inhibited using QVD, these changes in gene expression were completely blocked. This dependence on apoptosis for neighboring non-apoptotic cells to produce signals that promote tissue remodeling also occurs in response to focal ischemic injury in the brain and heart, indicating that osteoclastic bone remodeling follows a common paradigm for localized tissue repair.

Original languageEnglish (US)
Pages (from-to)132-137
Number of pages6
JournalBone
Volume64
DOIs
StatePublished - Jul 2014

Keywords

  • Apoptosis
  • In vivo fatigue
  • Osteoclasts
  • Osteocytes
  • Pan-caspase Inhibitor
  • RANKL

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Kennedy, O. D., Laudier, D. M., Majeska, R. J., Sun, H. B., & Schaffler, M. B. (2014). Osteocyte apoptosis is required for production of osteoclastogenic signals following bone fatigue in vivo. Bone, 64, 132-137. https://doi.org/10.1016/j.bone.2014.03.049