Oral Presentation 6th Australian Health and Medical Research Congress 2012

Osteomacs are multifunctional contributors to bone repair and dynamics. (#236)

Allison Pettit 1 , Ka Alexander 1 2 , S Kaur 1 , M E Wullschleger 3 , M K Ming 1 , L J Raggatt 1
  1. University of Queensland, Herston, QLD, Australia
  2. Queensland Institute of Medical Research, Herston, QLD, Australia
  3. Royal Brisbane and Women’s Hospital, Herston, QLD, Australia

Osteomacs are resident macrophages that are intercalated throughout bone lining tissues. We have uncovered that osteomacs make significant contributions to bone dynamics and repair. At active bone surfaces in mice, F4/80+ osteomacs are the predominant cell within the canopy structures formed over bone modeling and remodeling units. They are intimately associated with both osteoclasts and osteoblasts within these structures. While they share close lineage relationship to osteoclasts, evidence supports that osteomacs are not the preferred osteoclast precursor in vivo. However, bone marrow-derived macrophages (BMM) secrete factors that are able to greatly enhance RANKL-stimulate osteoclastogenesis. Similarly, BMM cultured in high calcium, secrete factors that promote osteoblast maturation and mineral deposition. In vivo depletion of macrophages/osteomacs lead to rapid and complete absence of osteoclacin+ osteoblast covered bone surfaces. Using a tibial injury model that heals via intramembranous ossification, we demonstrated that at least two macrophage populations, inflammatory and osteomacs, are associated with the repair response, with the latter enriched within sites of bone deposition. Depletion of macrophages/osteomacs halted the repair response, whether depletion was initiated at the time of surgery or delayed so that primary inflammatory events could occur unimpeded. Importantly repair could be accelerated through increasing osteomac numbers within the injury site via colony stimulating factor-1 treatment. Using an internally fixed femoral fracture model that heals via endochondral callus formation, we have similarly demonstrated that macrophages are widely distributed throughout the fracture site. Inflammatory macrophages were embedded within areas of early mesenchymal condensation. Osteomacs were located at the chondro-osseus junction during the transition from soft-hard callus. Depletion of macrophages either at the time of surgery or after the initial inflammatory events resulted in significant reduction in the magnitude of callus. A positive correlation was observed between callus size and residual F4/80+ macrophage number. Overall, the data implicate macrophages/osteomacs as important participants in bone repair via endochondral or intramembraneous ossification and represent an attractive and untapped therapeutic avenue for improving bone healing.