CD169(+) macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair

Lena Batoon, Susan Marie Millard, Martin Eduard Wullschleger, Corina Preda, Andy Chiu-Ku Wu, Simranpreet Kaur, Hsu-Wen Tseng, David Arthur Hume, Jean-Pierre Levesque, Liza Jane Raggatt, Allison Robyn Pettit

Research output: Contribution to journalArticlepeer-review

Abstract

Osteal macrophages (osteomacs) contribute to bone homeostasis and regeneration. To further distinguish their functions from osteoclasts, which share many markers and growth factor requirements, we developed a rapid, enzyme-free osteomac enrichment protocol that permitted characterization of minimally manipulated osteomacs by flow cytometry. Osteomacs differ from osteoclasts in expression of Siglec1 (CD169). This distinction was confirmed using the CD169-diphtheria toxin (DT) receptor (DTR) knock-in model. DT treatment of naïve CD169-DTR mice resulted in selective and striking loss of osteomacs, whilst osteoclasts and trabecular bone area were unaffected. Consistent with a previously-reported trophic interaction, osteomac loss was accompanied by a concomitant and proportionately striking reduction in osteoblasts. The impact of CD169(+) macrophage depletion was assessed in two models of bone injury that heal via either intramembranous (tibial injury) or endochondral (internally-plated femoral fracture model) ossification. In both models, CD169(+) macrophage, including osteomac depletion compromised bone repair. Importantly, DT treatment in CD169-DTR mice did not affect osteoclast frequency in either model. In the femoral fracture model, the magnitude of callus formation correlated with the number of F4/80(+) macrophages that persisted within the callus. Overall these observations provide compelling support that CD169(+) osteomacs, independent of osteoclasts, provide vital pro-anabolic support to osteoblasts during both bone homeostasis and repair.

Original languageEnglish
JournalBiomaterials
DOIs
Publication statusPublished - 22 Oct 2017

Keywords

  • Osteomac
  • Macrophage
  • Bone regeneration
  • Fracture repair
  • Bone formation
  • Osteoblast

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