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Cited by 476

The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.

Induction of Osteogenesis in Mesenchymal Stem Cells by Activated Monocytes/Macrophages Depends on Oncostatin M Signaling

Open access
Guihard, Pierre, Danger, Yannic, Brounais, Bénédicte, David, Emmanuelle, Brion, Régis, Delecrin, Joël, Richards, Carl D., Chevalier, Sylvie, Rédini, Françoise, Heymann, Dominique, Gascan, Hugues, Blanchard, Frédéric·2012·Stem Cells
DOI 10.1002/stem.1040
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Abstract

Bone resorption by osteoclasts and bone formation by osteoblasts are tightly coupled processes implicating factors in TNF, bone morphogenetic protein, and Wnt families. In osteoimmunology, macrophages were described as another critical cell population regulating bone formation by osteoblasts but the coupling factors were not identified. Using a high-throughput approach, we identified here Oncostatin M (OSM), a cytokine of the IL-6 family, as a major coupling factor produced by activated circulating CD14+ or bone marrow CD11b+ monocytes/macrophages that induce osteoblast differentiation and matrix mineralization from human mesenchymal stem cells while inhibiting adipogenesis. Upon activation of toll-like receptors (TLRs) by lipopolysaccharide or endogenous ligands, OSM was produced in classically activated inflammatory M1 and not M2 macrophages, through a cyclooxygenase-2 and prostaglandin-E2 regulatory loop. Stimulation of osteogenesis by activated monocytes/macrophages was prevented using neutralizing antibodies or siRNA to OSM, OSM receptor subunits gp130 and OSMR, or to the downstream transcription factor STAT3. The induced osteoblast differentiation program culminated with enhanced expression of CCAAT-enhancer-binding protein δ, Cbfa1, and alkaline phosphatase. Overexpression of OSM in the tibia of mice has led to new bone apposition with no sign of bone resorption. Two other cytokines have also a potent role in bone formation induced by monocytes/macrophages and activation of TLRs: IL-6 and leukemia inhibitory factor. We propose that during bone inflammation, infection, or injury, the IL-6 family signaling network activated by macrophages and TLR ligands stimulates bone formation that is largely uncoupled from bone resorption and is thus an important target for anabolic bone therapies. Disclosure of potential conflicts of interest is found at the end of this article.

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Metadata

Authors
Guihard, P., Danger, Y., Brounais, B., David, E., Brion, R., Delecrin, J., Richards, C. D., Chevalier, S., Rédini, F., Heymann, D., Gascan, H., & Blanchard, F.
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2012-03-22
Volume
30
Issue
4
Pages
762-772
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
DOI
10.1002/stem.1040
OpenAlex
W2020545615
Cited by
476
References
57
FWCI
10.57
Type
journal article
Language
en
Open access
bronze

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