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Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner

Fernandes, Tania J., Hodge, Jason M., Singh, Preetinder P., Eeles, Damien G., Collier, Fiona M., Holten, Ian, Ebeling, Peter R., Nicholson, Geoffrey C. and Quinn, Julian M. W. 2013, Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner, PLoS one, vol. 8, no. 9, pp. 1-13, doi: 10.1371/journal.pone.0073266.

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Title Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner
Author(s) Fernandes, Tania J.
Hodge, Jason M.
Singh, Preetinder P.
Eeles, Damien G.
Collier, Fiona M.
Holten, Ian
Ebeling, Peter R.
Nicholson, Geoffrey C.
Quinn, Julian M. W.
Journal name PLoS one
Volume number 8
Issue number 9
Article ID e73266
Start page 1
End page 13
Total pages 13
Publisher Public Library of Science
Place of publication San Francisco, Calif.
Publication date 2013-09
ISSN 1932-6203
Keyword(s) Cells, Cultured
Fetal Blood
Flow Cytometry
Glycoproteins
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Macrophages
Mesenchymal Stromal Cells
Osteoblasts
Real-Time Polymerase Chain Reaction
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
HUMAN BONE-MARROW
ADIPOSE-TISSUE
STROMAL CELLS
IN-VIVO
OSTEOCLAST DIFFERENTIATION
MULTIPLE ROLES
IDENTIFICATION
OSTEOGENESIS
GENERATION
RESORPTION
Summary In bone, depletion of osteoclasts reduces bone formation in vivo, as does osteal macrophage depletion. How osteoclasts and macrophages promote the action of bone forming osteoblasts is, however, unclear. Since recruitment and differentiation of multi-potential stromal cells/mesenchymal stem cells (MSC) generates new active osteoblasts, we investigated whether human osteoclasts and macrophages (generated from cord blood-derived hematopoietic progenitors) induce osteoblastic maturation in adipose tissue-derived MSC. When treated with an osteogenic stimulus (ascorbate, dexamethasone and β-glycerophosphate) these MSC form matrix-mineralising, alkaline phosphatase-expressing osteoblastic cells. Cord blood-derived progenitors were treated with macrophage colony stimulating factor (M-CSF) to form immature proliferating macrophages, or with M-CSF plus receptor activator of NFκB ligand (RANKL) to form osteoclasts; culture medium was conditioned for 3 days by these cells to study their production of osteoblastic factors. Both osteoclast- and macrophage-conditioned medium (CM) greatly enhanced MSC osteoblastic differentiation in both the presence and absence of osteogenic medium, evident by increased alkaline phosphatase levels within 4 days and increased mineralisation within 14 days. These CM effects were completely ablated by antibodies blocking gp130 or oncostatin M (OSM), and OSM was detectable in both CM. Recombinant OSM very potently stimulated osteoblastic maturation of these MSC and enhanced bone morphogenetic protein-2 (BMP-2) actions on MSC. To determine the influence of macrophage activation on this OSM-dependent activity, CM was collected from macrophage populations treated with M-CSF plus IL-4 (to induce alternative activation) or with GM-CSF, IFNγ and LPS to cause classical activation. CM from IL-4 treated macrophages stimulated osteoblastic maturation in MSC, while CM from classically-activated macrophages did not. Thus, macrophage-lineage cells, including osteoclasts but not classically activated macrophages, can strongly drive MSC-osteoblastic commitment in OSM-dependent manner. This supports the notion that eliciting gp130-dependent signals in human MSC would be a useful approach to increase bone formation.
Language eng
DOI 10.1371/journal.pone.0073266
Field of Research 110399 Clinical Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2013, Fernandes et al.
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30087254

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.