Skip to Main content Skip to Navigation
Journal articles

Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling.

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.
Complete list of metadatas

Cited literature [20 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00668995
Contributor : D* Heymann <>
Submitted on : Friday, July 20, 2012 - 7:00:14 AM
Last modification on : Monday, April 20, 2020 - 5:04:24 PM
Long-term archiving on: : Sunday, October 21, 2012 - 2:20:24 AM

File

Guihard_et_al.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Pierre Guihard, Yannic Danger, Bénédicte Brounais, Emmanuelle David, Régis Brion, et al.. Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling.. Stem Cells / Stem Cells (Miamisburg), Alphamed Press, 2012, 30 (4), pp.762-72. ⟨10.1002/stem.1040⟩. ⟨inserm-00668995⟩

Share

Metrics

Record views

463

Files downloads

772