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New Insights Into Osteoclast Biology

Authors
  • McDonald, Michelle Maree1, 2
  • Kim, Albert Sungsoo1, 2, 3, 4
  • Mulholland, Bridie S5, 5
  • Rauner, Martina6, 6
  • 1 Garvan Institute of Medical Research, Australia , (Australia)
  • 2 Faculty of Medicine UNSW Sydney, Australia , (Australia)
  • 3 Royal North Shore Hospital, Australia , (Australia)
  • 4 Westmead Hospital, Australia , (Australia)
  • 5 Griffith University, Australia , (Australia)
  • 6 Medical Faculty of the Technische Universität Dresden, Germany , (Germany)
Type
Published Article
Journal
JBMR Plus
Publisher
John Wiley & Sons, Inc.
Publication Date
Aug 30, 2021
Volume
5
Issue
9
Identifiers
DOI: 10.1002/jbm4.10539
PMID: 34532619
PMCID: PMC8441501
Source
PubMed Central
Keywords
Disciplines
  • Review
License
Unknown
External links

Abstract

Osteoclasts are multinucleated cells that are characterized by their unique ability to resorb large quantities of bone. Therefore, they are frequently the target of therapeutic interventions to ameliorate bone loss. In an adult organism, osteoclasts derive from hematopoietic stem cells and differentiate into osteoclasts within a multistep process under the influence of macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL). Historically, the osteoclast life cycle has been defined as linear, whereby lineage‐committed mononuclear precursors fuse to generate multinucleated highly specialized and localized bone phagocytic cells, which then undergo apoptosis within weeks. Recent advances through lineage tracing, single cell RNA sequencing, parabiosis, and intravital imaging approaches have challenged this dogma, revealing they have greater longevity and the capacity to circulate and undergo cell recycling. Indeed, these new insights highlight that under homeostatic conditions very few incidences of osteoclast apoptosis occur. More importantly, as we revisit the formation and fate of the osteoclast, novel methods to target osteoclast biology in bone pathology and regeneration are emerging. This review briefly summarizes the historical life cycle of osteoclasts and highlights recent discoveries made through advanced methodologies, which have led to a paradigm shift in osteoclast biology. These findings are discussed in light of both existing and emerging bone targeted therapeutics, bone pathologies, and communication between osteoclasts and cells resident in bone or at distant sites. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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