Osteomacs are Critical for Optimal Intramembranous Bone Formation in a Tibial Defect Model of Bone Healing

Alexander, K. A., Raggatt, L., Chang, M., Maylin, E., Muller, R., Kohler, T., Wu, A., Hume, D. and Pettit, A. (2009). Osteomacs are Critical for Optimal Intramembranous Bone Formation in a Tibial Defect Model of Bone Healing. In: Journal of Bone and Mineral Research. Australian Society of Bone and Mineral Research (ASBMR) 31st Annual Meeting, Denver, Colorado, USA, (). 11-15 September, 2009.

Author Alexander, K. A.
Raggatt, L.
Chang, M.
Maylin, E.
Muller, R.
Kohler, T.
Wu, A.
Hume, D.
Pettit, A.
Title of paper Osteomacs are Critical for Optimal Intramembranous Bone Formation in a Tibial Defect Model of Bone Healing
Conference name Australian Society of Bone and Mineral Research (ASBMR) 31st Annual Meeting
Conference location Denver, Colorado, USA
Conference dates 11-15 September, 2009
Proceedings title Journal of Bone and Mineral Research   Check publisher's open access policy
Place of Publication United States
Publisher American Society for Bone and Mineral Research
Publication Year 2009
Sub-type Oral presentation
ISSN 1523-4681
Volume 24
Issue Supp. 1
Language eng
Formatted Abstract/Summary
Osteal tissues contain a resident population of macrophages (osteomacs) and in vitro these cells regulate osteoblast mineralisation. In vivo osteomacs form a canopy structure covering osteoblast bone forming surfaces (ObS) and depletion of osteomacs, using the Macrophage-Fas-Induced Apoptosis (Mafia) transgenic mouse, induces complete loss of ObS at sites of bone modelling. To confirm the requirement of osteomacs for in vivo bone formation a stabilised tibial defect model was employed in which the defect site fills with woven bone via intramembranous ossification 7 days post surgery. Immunohistochemistry demonstrated that F4/80+ osteomacs accumulated within the defect site and formed the unique canopy structure over collagen type I (CT1)+ osteoblasts on new woven bone surfaces. Osteotomies were performed in Mafia mice and a single injection of ligand or vehicle was administered intra-defect at the time of surgery to locally deplete osteomacs. Ligand treated animals demonstrated a striking reduction in F4/80+ osteomacs and CT1+ osteoblasts within the defect. Quantitative μCT analysis confirmed significantly less woven bone deposited (BV/TV) 7 days post surgery in ligand treated (14.96±3.3%) compared to vehicle (35.74±8.3%) treated mice, and by 9 days post surgery the difference between ligand (19.17±5.1%) and vehicle (65.08±4.12%) treated mice was even more pronounced. This demonstrates that osteomacs are critical for new intramembranous woven bone deposition. Osteoclasts may also be susceptible to apoptosis in ligand treated Mafia mice. To confirm that the decreased bone formation was due to a loss of osteomacs not osteoclasts, osteotomies were performed in osteoprotegerin (OPG) treated mice. No change in woven bone deposition or defect healing was observed in OPG treated mice confirming that it is the osteomacs that play a critical role in driving and maintaining osteoblast function at sites of intramembranous bone deposition during bone healing. The differentiation, proliferation and survival of macrophages are dependent on the cytokine colony-stimulating factor 1 (CSF-1), we administered CSF-1 via an intra-defect injection during surgery. Immunohistochemistry demonstrated that CSF-1 treatment increased F4/80+ osteomacs within the defect site, the bone marrow cavity and the surrounding periosteum, suggesting that targeting osteomacs may prove to be a valid therapeutic approach to improving bone repair.
Subjects 11 Medical and Health Sciences
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes abstract number: A09002427

Document type: Conference Paper
Collection: Institute for Molecular Bioscience - Publications
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Created: Tue, 05 Oct 2010, 11:36:30 EST by Laura McTaggart on behalf of Institute for Molecular Bioscience